- Identification and synthesis of selective cholesterol esterase inhibitor using dynamic combinatorial chemistry
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In this study, the concept of dynamic combinatorial chemistry (DCC) was applied to explore novel cholesterol esterase (CEase) inhibitors. In the presence of enzyme, two substrates (A1H3 and A2H3) were amplified from the dynamic combinatorial library (DCL), which was generated through reversible acylhydrazone formation reaction. In the in vitro biological evaluation, compound A1H3 exhibited not only potent (IC50 in nanomolar range) but also selective inhibition (>120 folds of selectivity for CEase over AChE). Furthermore, the binding pattern and possible binding mechanism were investigated in the kinetic experiment and molecular docking study, respectively.
- Zhao, Shuang,Wu, Yao,Hu, Lei
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- Design, docking, synthesis, and characterization of novel N'(2-phenoxyacetyl) nicotinohydrazide and N'(2-phenoxyacetyl)isonicotinohydrazide derivatives as anti-inflammatory and analgesic agents
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Inflammation is the complex biological response of vascular tissues, which is partly determined by prostaglandins (PLA2). The cyclooxygenase (COX) enzyme exists in two isoforms: COX-1 and COX-2 and by the action of this, the PGs are produced. Besides, nonsteroidal anti-inflammatory drugs (NSAIDs) are therapeutic agents useful in the treatment of inflammation. Encouraged by this, the new derivatives of N'(2-phenoxyacetyl)nicotinohydrazide 9(a-e) and N'(2-phenoxyacetyl)isonicotinohydrazide 10(a-e) were designed, synthesized, characterized, and identified as remarkable anti-inflammatory and analgesic agents. These compounds were prepared in a series of steps starting with different phenol derivatives. Among the series, compound (10e) showed the highest IC50 value for COX-1 inhibition, whereas compounds (9e) and (10e) exhibited the highest COX-2SI. Further, molecular Docking Studies have been performed for the potent compound to check the three-dimensional geometrical view of the ligand binding to the targeted enzymes.
- Al-Ostoot, Fares Hezam,Khanum, Shaukath Ara,M, Pallavi H,Vivek, Hamse Kameshwar
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- Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)
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Histone Deacetylases (HDACs) are among the most attractive and interesting targets in anticancer drug discovery. The clinical relevance of HDAC inhibitors (HDACIs) is testified by four FDA-approved drugs for cancer treatment. However, one of the main drawbacks of these drugs resides in the lack of selectivity against the different HDAC isoforms, resulting in severe side effects. Thus, the identification of selective HDACIs represents an exciting challenge for medicinal chemists. HDACIs are composed of a cap group, a linker region, and a metal-binding group interacting with the catalytic zinc ion. While the cap group has been extensively investigated, less information is available about the effect of the linker on isoform selectivity. To this aim, in this work, we explored novel linker chemotypes to direct isoform selectivity. A small library of 25 hydroxamic acids with hitherto unexplored linker chemotypes was prepared. In vitro tests demonstrated that, depending on the linker type, some candidates selectively inhibit HDAC1 over HDAC6 isoform or vice versa. Docking calculations were performed to rationalize the effect of the novel linker chemotypes on biologic activity. Moreover, four compounds were able to increase the levels of acetylation of histone H3 or tubulin. These compounds were also assayed in breast cancer MCF7 cells to test their antiproliferative effect. Three compounds showed a significant reduction of cancer proliferation, representing valuable starting points for further optimization.
- Linciano, Pasquale,Benedetti, Rosaria,Pinzi, Luca,Russo, Fabiana,Chianese, Ugo,Sorbi, Claudia,Altucci, Lucia,Rastelli, Giulio,Brasili, Livio,Franchini, Silvia
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- (Trifluoromethylselenyl)methylchalcogenyl as Emerging Fluorinated Groups: Synthesis under Photoredox Catalysis and Determination of the Lipophilicity
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The synthesis of molecules bearing (trifluoromethylselenyl)methylchalcogenyl groups is described via an efficient two-step strategy based on a metal-free photoredox catalyzed decarboxylative trifluoromethylselenolation with good yields up to 88 %, which raised to 98 % in flow chemistry conditions. The flow methods allowed also to scale up the reaction. The mechanism of this key reaction was studied. The physicochemical characterization of these emerging groups was performed by determining their Hansch–Leo lipophilicity parameters with high values up to 2.24. This reaction was also extended to perfluoroalkylselenolation with yields up to 95 %. Finally, this method was successfully applied to the functionalization of relevant bioactive molecules such as tocopherol or estrone derivatives.
- Grollier, Kevin,De Zordo-Banliat, Arnaud,Bourdreux, Flavien,Pegot, Bruce,Dagousset, Guillaume,Magnier, Emmanuel,Billard, Thierry
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supporting information
p. 6028 - 6033
(2021/03/15)
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- Expedient discovery for novel antifungal leads: 1,3,4-Oxadiazole derivatives bearing a quinazolin-4(3H)-one fragment
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Developing novel fungicide candidates are intensively promoted by the rapid emergences of resistant fungi that outbreak on agricultural production. Aiming to discovery novel antifungal leads, a series of 1,3,4-oxadiazole derivatives bearing a quinazolin-4(3H)-one fragment were constructed for evaluating their inhibition effects against phytopathogenic fungi in vitro and in vivo. Systematically structural optimizations generated the bioactive molecule I32 that was identified as a promising inhibitor against Rhizoctonia solani with the in vivo preventative effect of 58.63% at 200 μg/mL. The observations that were captured by scanning electron microscopy and transmission electron microscopy demonstrated that the bioactive molecule I32 could induce the sprawling growth of hyphae, the local shrinkage and rupture on hyphal surfaces, the extreme swelling of vacuoles, the striking distortions on cell walls, and the reduction of mitochondria numbers. The above results provided an indispensable complement for the discovery of antifungal lead bearing a quinazolin-4(3H)-one and 1,3,4-oxadiazole fragment.
- Chai, Jianqi,Chen, Min,Jin, Fei,Kong, Xiangyi,Wang, Xiaobin,Xue, Wei,Yang, Chunlong
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- Modulation of DNA damage response by targeting ATM kinase using newly synthesized di-phenoxy acetamide (DPA) analogs to induce anti-neoplasia
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Background: Imbalance and instability in the structure of the DNA have become major characteristics of cancer. In response to DNA damage, DNA damage response (DDR) protein, ataxia telangiectasia mutated (ATM), plays a pivotal role in the modulation of regulatory regions responsible for inhibition of apoptosis, thereby neoplastic progression. Methods: A new series of DPA (7a–t) were synthesized, characterized. Anti-proliferative studies to identify the lead compound were carried out by LDH and MTT assay. Apoptosis/DNA damage was measured through FACS, Annexin-v staining, TUNEL and Comet assay. Elucidation of molecular mechanism through immunoblot and further validation of the drug effect through in vivo approaches. Results: Initial in vitro anti-proliferative screening of Compounds DPA (7a–t) against multiple cancer cell lines identified Compound DPA (7n) as a potent cytotoxic molecule with IC50 value of 4.3?μM. Down the line, in vitro and in vivo evaluation of Compound DPA (7n) inferred that it has apoptotic inducing potentiality. Further, evaluation of molecular mechanism inferred that Compound DPA (7n) effectively modulates ATM phosphorylation only, eventually altering downstream signalling pathways. Conclusions: Compound DPA (7n) emerged as a potent proapoptotic and anti-neoplastic agent by inhibiting ATM kinase activity both in vitro and in vivo. The conferring results ascertain that the drug could be developed as a new ATM kinase inhibitor with anti-cancer capacity. Graphic abstract: [Figure not available: see fulltext.]
- Al-Ostoot, Fares Hezam,Sherapura, Ankith,Malojirao, Vikas H.,Thirusangu, Prabhu,Al-Muhimeed, Tahani I.,Khanum, Shaukath Ara,Prabhakar
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p. 1344 - 1360
(2021/06/14)
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- Targeting HIF-1α by newly synthesized Indolephenoxyacetamide (IPA) analogs to induce anti-angiogenesis-mediated solid tumor suppression
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Background: Hypoxic microenvironment is a common feature of solid tumors, which leads to the promotion of cancer. The transcription factor, HIF-1α, expressed under hypoxic conditions stimulates tumor angiogenesis, favoring HIF-1α as a promising anticancer agent. On the other hand, synthetic Indolephenoxyacetamide derivatives are known for their pharmacological potentiality. With this background here, we have synthesized, characterized, and validated the new IPA (8a–n) analogs for anti-tumor activity. Methods: The new series of IPA (8a–n) were synthesized through a multi-step reaction sequence and characterized based on the different spectroscopic analysis FT-IR, 1H, 13C NMR, mass spectra, and elemental analyses. Cell-based screening of IPA (8a–n) was assessed by MTT assay. Anti-angiogenic efficacy of IPA (8k) validated through CAM, Rat corneal, tube formation and migration assay. The underlying molecular mechanism is validated through zymogram and IB studies. The in vivo anti-tumor activity was measured in the DLA solid tumor model. Results: Screening for anti-proliferative studies inferred, IPA (8k) is a lead molecule with an IC50 value of ?5?μM. Anti-angiogenic assays revealed the angiopreventive activity through inhibition of HIF-1α and modulation downstream regulatory genes, VEGF, MMPs, and P53. The results are confirmative in an in vivo solid tumor model. Conclusion: The IPA (8k) is a potent anti-proliferative molecule with anti-angiogenic activity and specifically targets HIF1α, thereby modulates its downstream regulatory genes both in vitro and in vivo. The study provides scope for new target-specific drug development against HIF-1α for the treatment of solid tumors. Graphic abstract: [Figure not available: see fulltext.].
- Al-Ostoot, Fares Hezam,Sherapura, Ankith,V, Vigneshwaran,Basappa, Giridhara,H.K, Vivek,B.T, Prabhakar,Khanum, Shaukath Ara
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p. 1328 - 1343
(2021/05/03)
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- Drastic fluorine effect: Complete reversal of the selectivity in the Au-catalyzed hydroalkoxylation reaction of fluorinated haloalkynes
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The gold-catalyzed hydration reaction of haloalkynes is highly regioselective producing 2-halomethylketones as the sole products. Herein, we document a drastic fluorine effect where the reaction of 1-halo-3,3-difluoroalkynes as substrates leads to a complete reversal of selectivity and produces 3,3-difluoroesters as the unique products.
- Cloutier, Mélissa,Mamone, Marius,Paquin, Jean-Fran?ois
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supporting information
p. 5969 - 5972
(2020/06/04)
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- Design and synthesis of α-phenoxy-N-sulfonylphenyl acetamides as Trypanosoma brucei Leucyl-tRNA synthetase inhibitors
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Human African trypanosomiasis (HAT), caused by the parasitic protozoa Trypanosoma brucei, is one of the fatal diseases in tropical areas and current medicines are insufficient. Thus, development of new drugs for HAT is urgently needed. Leucyl-tRNA synthetase (LeuRS), a recently clinically validated antimicrobial target, is an attractive target for development of antitrypanosomal drugs. In this work, we report a series of α-phenoxy-N-sulfonylphenyl acetamides as T. brucei LeuRS inhibitors. The most potent compound 28g showed an IC50 of 0.70 μM which was 250-fold more potent than the starting hit compound 1. The structure-activity relationship was also discussed. These acetamides provided a new scaffold and lead compounds for the further development of clinically useful antitrypanosomal agents.
- Xin, Weixiang,Li, Zezhong,Wang, Qing,Du, Jin,Zhu, Mingyan,Zhou, Huchen
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- Cobalt Nanoparticles-Catalyzed Widely Applicable Successive C?C Bond Cleavage in Alcohols to Access Esters
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Selective cleavage and functionalization of C?C bonds have important applications in organic synthesis and biomass utilization. However, functionalization of C?C bonds by controlled cleavage remains difficult and challenging because they are inert. Herein, we describe an unprecedented efficient protocol for the breaking of successive C?C bonds in alcohols to form esters with one or multiple carbon atoms less using heterogeneous cobalt nanoparticles as catalyst with dioxygen as the oxidant. A wide range of alcohols including inactive long-chain alkyl aryl alcohols undergo smoothly successive cleavage of adjacent ?(C?C)n? bonds to afford the corresponding esters. The catalyst was used for seven times without any decrease in activity. Characterization and control experiments disclose that cobalt nanoparticles are responsible for the successive cleavage of C?C bonds to achieve excellent catalytic activity, while the presence of Co-Nx has just the opposite effect. Preliminary mechanistic studies reveal that a tandem sequence reaction is involved in this process.
- Dai, Wen,Gao, Shuang,Li, Guosong,Luo, Huihui,Lv, Ying,Shang, Sensen,Wang, Lianyue
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supporting information
p. 19268 - 19274
(2020/08/26)
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- Identification of a Novel Oxadiazole Inhibitor of Mammalian Target of Rapamycin
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We performed a biochemical screen against mTOR using in-house small molecule library. Two novel, structurally distinct hits were identified. Among them, a novel oxadiazole scaffold compound (2) suppressed the phosphorylation of both S6K1 and Akt1 in HeLa cells. Docking study suggested that 2 is ATP-competitive and shows a pi-pi interaction with Trp2239 and hydrogen bonds with Trp2239 and Thr2245. Through derivatization, a slightly more potent analogue (2a) was identified with IC50 of 9.6 μM. Our study provides a starting point for discovery of novel potent mTOR inhibitors.
- Lim, Sunwoo,Lee, Hyomin,Kim, Euijung,Hur, Wooyoung
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p. 296 - 303
(2020/02/04)
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- Synthesis and luminescence properties of novel 8-hydroxyquinoline derivatives and their Eu(III) complexes
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Six novel 8-hydroxyquinoline derivatives were synthesized using 2-methyl-8-hydroxyquinoline and para-substituted phenol as the main starting materials, and were characterized by 1H nuclear magnetic resonance (NMR), mass spectrometry (MS), ultraviolet (UV) light analysis and infra-red (IR) light analysis. Their complexes with Eu(III) were also prepared and characterized by elemental analysis, molar conductivity, UV light analysis, IR light analysis, and thermogravimetric–differential thermal analysis (TG–DTA). The results showed that the ligand coordinated well with Eu(III) ions and had excellent thermal stability. The structure of the target complex was EuY1–6(NO3)3.2H2O. The luminescence properties of the target complexes were investigated, the results indicated that all target complexes had favorable luminescence properties and that the introduction of an electron-donating group could enhance the luminescence intensity of the corresponding complexes, but the addition of an electron-withdrawing group had the opposite effect. Among all the target complexes, the methoxy-substituted complex (–OCH3) had the highest fluorescence intensity and the nitro-substituted complex (–NO2) had the weakest fluorescence intensity. The results showed that 8-hydroxyquinoline derivatives had good energy transfer efficiency for the Eu(III) ion. All the target complexes had a relatively high fluorescence quantum yield. The fluorescence quantum yield of the complex EuY3(NO3)3.2H2O was highest among all target complexes and was up to 0.628. Because of excellent luminescence properties and thermal stabilities of the Eu(III) complexes, they could be used as promising candidate luminescent materials.
- Wu, Yongqiang,Guo, Tiantong,Shu, Dehua,Zhang, Wu,Luan, Fangfei,Shi, Ling,Guo, Dongcai
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p. 855 - 862
(2018/07/13)
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- 1,2,4-Triazole-based benzothiazole/benzoxazole derivatives: Design, synthesis, p38α MAP kinase inhibition, anti-inflammatory activity and molecular docking studies
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Novel N-(benzothiazol/oxazol-2-yl)-2-[(5-(phenoxymethyl)-4-aryl-4H-1,2,4-triazol-3-yl)thio] acetamide derivatives (5a-n) were synthesized and investigated for in vitro anti-inflammatory activity and p38α MAP kinase inhibition. Compounds showing good in vitro activities (5a, 5b, 5d, 5e, 5i, 5k and 5l) were studied for their in vivo anti-inflammatory activity using carrageenan induced rat paw edema model. Compound 5b emerged as the most active compound with an edema inhibition of 84.43%. It also showed improved GI safety profile with lower ulcer severity index and lipid peroxidation potential. Also, p38α MAP kinase assay of 5b showed superior inhibitory potency (IC50:0.031 ± 0.14 μM) than the standard SB 203580 (IC50:0.043 ± 0.14 μM). To predict their binding mode compounds were also docked against p38α MAP kinase enzyme. Compound 5b and SB 203580 showed hinge region interaction with MET 109.
- Tariq, Sana,Kamboj, Payal,Alam, Ozair,Amir, Mohd.
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p. 630 - 641
(2018/09/29)
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- Evaluating Gold and Selenium Chemistry for Selective Transformations of Lignin Model Compounds
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Applications of gold and selenium chemistry are reported as novel approaches to promote lignin depolymerization into more valuable chemicals via selective oxidation reactions (alcohol oxidations and Baeyer-Villiger reactions). In this study, we proposed two different oxidative methodologies using Au/SiO2 and phenylseleninic acid resin (PAR) as stable and reusable catalysts to promote selective transformations of the β-O-4 linkage of lignin model compounds. After evaluating the catalytic systems under batch conditions, they were both applied in a packed-bed reactor for continuous flow operations. By using Au/SiO2 as a catalyst under flow conditions, ketones were efficiently obtained (up to 86% conversion) from the oxidation of alcohols with a residence time (tR) of 30 min. In the case of Baeyer-Villiger oxidations catalyzed by phenylseleninic acid resin, the corresponding esters were obtained in up to 91% conversion (tR=30 min). Both systems efficiently catalyzed the conversion of the lignin model compounds. (Figure presented.).
- Santos, Wagner C. C.,Dias, Kevin A.,Santos, Leidaiany P.,Kisukuri, Camila M.,Rodrigues, Thenner S.,Geonmonond, Rafael S.,Camargo, Pedro H. C.,Andrade, Leandro H.
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supporting information
p. 1376 - 1383
(2018/02/13)
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- The synthesis and evaluation of phenoxyacylhydroxamic acids as potential agents for Helicobacter pylori infections
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Two series of ω-phenoxy contained acylhydroxamic acids as novel urease inhibitors were designed and synthesized. Biological activity evaluations revealed that ω-phenoxypropinoylhydroxamic acids were more active than phenoxyacetohydroxamic acids. Out of these compounds, 3-(3,4-dichlorophenoxy)propionylhydroxamic acid c24 showed significant potency against urease in both cell free extract (IC50 = 0.061 ± 0.003 μM) and intact cell (IC50 = 0.89 ± 0.05 μM), being over 450- and 120-fold more potent than the clinically prescribed urease inhibitor AHA, repectively. Non-linear fitting of experimental data (V-[S]) suggested a mixed-type inhibition mechanism and a dual site binding mode of these compounds.
- Ni, Wei-Wei,Liu, Qi,Ren, Shen-Zhen,Li, Wei-Yi,Yi, Li-Li,Jing, Heng,Sheng, Li-Xin,Wan, Qin,Zhong, Ping-Fu,Fang, Hai-Lian,Ouyang, Hui,Xiao, Zhu-Ping,Zhu, Hai-Liang
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supporting information
p. 4145 - 4152
(2018/07/13)
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- Transition-metal-free conversion of lignin model compounds to high-value aromatics: Scope and chemoselectivity
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An efficient and straightforward reaction protocol for the conversion of lignin model compounds was developed based on a simple system consisting of a base, oxygen, and a green solvent under mild conditions in the absence of metals. This protocol was successfully applied to the cleavage of both 'β-O-4' dimeric and trimeric compounds, and a controlled selective degradation was achieved depending on the bond type. The feasibility of this method to provide aromatic compounds in high yields from lignin by a sequential oxidative dehomologation reaction was clearly demonstrated.
- Lee, Tae Woo,Yang, Jung Woon
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p. 3761 - 3771
(2018/08/21)
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- Carbene Transfer and Carbene Insertion Reactions Catalyzed by a Mixed-Ligand Copper(I) Complex
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The catalytic activity of the mixed-ligand copper(I) complex [Cu(PPh3)2(κ2-O,O"-lact)] (1) {lact = l-(+)-lactate} has been investigated in carbene transfer and carbene insertion reactions. Complex 1 catalytically promoted the diastereoselective cyclopropanation of olefins in the presence of ethyl diazoacetate (EDA), under mild conditions, and with a low catalyst loading (1 mol-%). In the case of internal alkenes, a trans/cis ratio of up to 93:7 was reached. Moreover, compound 1 easily promoted the insertion of the carbene fragment deriving from the decomposition of ethyl diazoacetate into O–H (alcohols and phenols) and N–H (amine) bonds, with formation of the corresponding ethyl 2-alkoxyacetate, ethyl 2-phenoxyacetate, and ethyl 2-aminoacetate derivatives in good to high yields.
- Brenna, Stefano,Ardizzoia, G. Attilio
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p. 3336 - 3342
(2018/07/13)
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- The Novel 4-Phenyl-2-Phenoxyacetamide Thiazoles modulates the tumor hypoxia leading to the crackdown of neoangiogenesis and evoking the cell death
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Tumor microenvironment is a complex multistep event which involves several hallmarks that transform the normal cell into cancerous cell. Designing the novel antagonistic molecule to reverse the tumor microenvironment with specific target is essential in modern biological studies. The novel 4-phenyl-2-phenoxyacetamide thiazole analogues 8a-ab were synthesized in multistep process, then screened and assessed for cytotoxic and anti-proliferative effects in vitro against multiple cancer cells of different origin such as MCF-7, A549, EAC and DLA cells which revealed that compound 8f with fluoro and methyl substitute has potential cytotoxic efficacy with an average IC50 value of ? 13 μM. The mechanism of cytotoxicity assessed for anti-tumor studies both in ascites and solid tumor models in-vivo inferred the regressed tumor activity. This is due to changes in the cause of tumor microenvironment with crackdown of neovascularization and evoking apoptosis process as assessed by CAM, corneal vascularization and apoptotic hallmarks in 8f treated cells. The molecular gene studies inferred involvement of HIF-1upregulation and stabilization of p53 which are interlinked in signaling as conferred by immunoblot analysis.
- Mohammed, Yasser Hussein Eissa,Malojirao, Vikas H.,Thirusangu, Prabhu,Al-Ghorbani, Mohammed,Prabhakar,Khanum, Shaukath Ara
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p. 1826 - 1839
(2017/11/16)
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- Synthesis and larvicidal activity of 1,3,4-oxadiazole derivatives containing a 3-chloropyridin-2-yl-1H-pyrazole scaffold
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Abstract: A new series of 1,3,4-oxadiazole derivatives with a 3-chloropyridin-2-yl-1H-pyrazole moiety was designed, synthesized, and characterized. The results of bioassay against Helicoverpa armigera and Plutella xylostella indicated that some of the synthesized compounds showed remarkable larvicidal activity. In particular, the LC50 values of the most active compounds against P. xylostella were 46.5, 23.9, and 13.9?mg/dm3, and against Helicoverpa armigera were 88.3 and 69.5?mg/dm3, the latter being slightly better than commercial chlorpyrifos (LC50 103.77?mg/dm3). Preliminary SAR was also discussed. Graphical abstract: [Figure not available: see fulltext.].
- Wang, Yanyan,Lu, Xiumian,Shi, Jun,Xu, Jiahong,Wang, Fenghua,Yang, Xiao,Yu, Gang,Liu, Zhiqian,Li, Chuanhui,Dai, Ali,Zhao, Yonghui,Wu, Jian
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p. 611 - 623
(2018/01/17)
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- Tirfluoromethylpyridine oxadiazoles (ether)derivative and application thereof
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The invention discloses an application of a tirfluoromethylpyridine oxadiazole (ether)derivative in a pesticide. A structure is shown as a general formula I, a compound shown in the general formula Ihas good insecticidal activity, and can be used for controlling insects such as diamondback moth and armyworm. The compound has excellent control effect for insects such as diamondback moth and armyworm, and also has control effect for the insects having resistance to the traditional pesticides, in addition, introduction of fluorine-containing groups such as tirfluoromethylpyridine and oxadiazoleas well as heterocyclic ring can enhance a rate for forming hydrogen bond effect between a compound and a target, and the activity of the compound is increased.
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Paragraph 0128-0132; 0136-0140; 0144-0148
(2018/07/30)
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- Synthesis, Nematicidal Activity, and 3D-QSAR of Novel 1,3,4-Oxadiazole/ Thiadiazole Thioether Derivatives
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Forty one novel 1,3,4-oxadiazole/thiadiazole thioether derivatives containing phenoxy moiety were designed and synthesized. Bioassay demonstrated that some of them showed remarkable activities against Tylenchulus semipenetrans in vitro and in vivo. Compounds 20, 21, 35 and 39 showed excellent lethal activities after treatment for 48?h in vitro, with LC50 values of 13.4?±?1.8, 11.7?±?2.5, 13.7?±?2.4 and 13.3?±?1.1?mg·L–1, respectively, which were obviously superior to fosthiazate (49.1?±?2.8?mg·L–1) and avermectin (26.6?±?2.3?mg·L–1). Compound 21 can effectively control the citrus nematode disease caused by T. semipenetrans at 200?mg·L–1 in vivo with (68?±?3)% inhibitory effect, which was even better than that of avermectin ((63?±?2)%). The CoMFA and CoMSIA models of three-dimensional quantitative structure-activity relationships (3D-QSARs) were established. The compound 33 was designed based on the 3D-QSAR models with more vigorous nematicidal activities in vitro (LC50?=?9.8?±?1.4?mg·L–1) and in vivo ((70?±?5)%). These results demonstrated that compound 33 can be considered as a potential nematicide.
- Chen, Jixiang,Gan, Xiuhai,Yi, Chongfen,Wang, Shaobo,Yang, Yuyuan,He, Fangcheng,Hu, Deyu,Song, Baoan
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p. 939 - 944
(2018/09/22)
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- Preparation method of 2,4-dichlorophenoxyacetic acid and salt thereof
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The invention provides a preparation method of 2,4-dichlorophenoxyacetic acid and a salt thereof, wherein the preparation method includes the following steps: S1) carrying out a reaction of phenol andchloracetic ester under alkaline conditions to obtain phenoxyacetic ester; S2) carrying out selective chlorination reaction of the phenoxyacetic ester with a chlorinating agent under the action of acatalyst A and a catalyst B to obtain 2,4-dichlorophenoxyacetic ester, wherein the catalyst A is Lewis acid, and the catalyst B is C5-22 thioethers, thiazoles, isothiazoles and thiophenes or halogenated derivatives thereof; and S3) carrying out hydrolysis reaction of 2,4-dichlorophenoxyacetic ester under acidic conditions to obtain 2,4-dichlorophenoxyacetic acid; or after 2,4-dichlorophenoxyaceticester is obtained, carrying out an alkaline hydrolysis reaction with an alkaline compound to obtain 2,4-dichlorophenoxyacetate. The production and use of 2,4-dichlorophenol with unpleasant odor are avoided, the production of dioxins is eliminated, the yield of products is improved, and the output of three wastes is greatly reduced.
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Paragraph 0103; 0104
(2019/01/06)
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- Preparation method of phenoxycarboxylic acid choline salt
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The invention provides a preparation method of a phenoxycarboxylic acid choline salt, wherein the preparation method includes the steps: S1, carrying out condensation reaction of phenol or o-cresol with chlorocarboxylic ester in the presence of alkaline substances to obtain phenoxycarboxylic ester; S2, carrying out selective chlorination of the phenoxycarboxylic ester with a chlorinating agent inthe presence of a first catalyst and a second catalyst to obtain chlorobenzoxycarboxylic ester; and S3, after reaction of trimethylamine with ethylene oxide, adding the chlorophenoxycarboxylic acid ester, and carrying out alkaline hydrolysis reaction to obtain the phenoxycarboxylic acid choline salt. Compared with a conventional synthesis technology, the preparation method effectively avoids the production and use of chlorophenols with unpleasant odor, radically eliminates the production of highly toxic dioxins, and greatly improves the product quality and the operation environment of the production site; with phenol as the raw material, through condensation, selective chlorination and alkaline hydrolysis, the high-quality phenoxycarboxylic acid choline salt is obtained, the loss of effective ingredients is effectively avoided and the yield of the product is increased.
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Paragraph 0075-0076
(2019/01/08)
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- Carbene X[sbnd]H bond insertions catalyzed by copper(I) macrocyclic pyridine-containing ligand (PcL) complexes
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A catalytic system comprising copper(I) and macrocyclic pyridine-containing ligands (Pc-L) proves capable of promoting carbene Si[sbnd]H bond insertions using diazo compounds as the carbene source. This catalytic system showed broad scope and a remarkable robustness as indicated by high TON numbers (up to 30000). Moreover, the use of enynones as carbene sources proved also feasible in hydrosilane insertion using this catalytic system. Finally, the insertion in O[sbnd]H and N[sbnd]H bonds of phenols and anilines, respectively, has been also demonstrated.
- Tseberlidis, Giorgio,Caselli, Alessandro,Vicente, Rubén
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supporting information
p. 1 - 5
(2017/03/01)
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- Highly effective C-C bond cleavage of lignin model compounds
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A highly effective method is developed for the C-C bond cleavage of lignin model compounds. The inert Cα-Cβ or Cα-Cphenyl bond of oxidized lignin model compounds was successfully converted to an active ester bond through the classic organic name reaction, Baeyer-Villiger (BV) oxidation, and thus acetal esters and aryl esters were produced in high yields (up to 99%) at room temperature. Next, K2CO3 catalyzed the alcoholysis of the resulting ester products at 45 °C, affording various useful chemical platforms in excellent yields (up to 99%), such as phenols and multifunctional esters. This method uses commercially available reagents, is transition-metal free and simple, but highly effective, and involves mild reaction conditions.
- Wang, Yinling,Wang, Qianyi,He, Jianghua,Zhang, Yuetao
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supporting information
p. 3135 - 3141
(2017/07/24)
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- Isoflavone amide derivatives, their preparation method and medical use
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The invention belongs to the field of medicinal chemistry, and relates to derivatives of isoflavones amides, as well as a preparation method and medical application of derivatives, in particular to the derivatives of the isoflavones amides with the general formula of (I) shown as the specification, the preparation method and the medical application of the derivatives, particularly the application of the derivatives of the isoflavones amides serving as medicaments for preventing or treating hyperlipemia, adiposis or type-II diabetes.
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Paragraph 0059; 0063; 0064; 0065
(2017/08/31)
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- The anti-invasive role of novel synthesized pyridazine hydrazide appended phenoxy acetic acid against neoplastic development targeting matrix metallo proteases
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Neoplastic metastasis is a major process where tumor cells migrate from the primary tumor and colonize at other parts of our body to form secondary tumor. Cancer incidences are rising and novel anti-neoplastic compounds with new mechanism of actions are essential for preventing cancer related deaths. In the current examination, a novel series of pyridazine analogues 6a-l was synthesized and evaluated against metastatic neoplastic cells. Experimental data postulated compound 6j has potential cytotoxic efficacy with prolonged activity against various cancer cells, including A549, HepG2, A498, CaSki and SiHa cells. Moreover, compound 6j arrests the A549 migration and invasions markedly by counteracting matrix metalloproteinase (MMP)-2 and MMP-9 expressions. Also, compound 6j proved its potentiality against Dalton's solid lymphoma progression in-vivo by abridging MVD and MMP expressions. Compound 6j interacts with MMP-2 and MMP-9 by H- bond in-silico, thereby down regulates the MMPs action in tumourigenesis. Altogether, we concluded that compound 6j down regulates MMP-2 and MMP-9 and thereby impairs metastatic cancer cell migration and invasions which can be translated into a potent anti-neoplastic agent.
- Eissa Mohammed, Yasser Hussein,Thirusangu, Prabhu,Zabiulla,Vigneshwaran,B.T, Prabhakar,Khanum, Shaukath Ara
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p. 375 - 386
(2017/09/02)
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- A novel C - aryl glucoside SGLT2 inhibitor
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The invention discloses a new C-aryl glycosidase SGLT2 (sodium glucose transporter type-2) inhibitor, relates to the field of medicines associated with diabetes, and in particular relates to a new C-aryl glycosidase derivative shown as the general formula (I), a preparation method thereof, compositions thereof, and use thereof in preparing hypoglycemic drugs. The C-aryl glucoside derivative has excellent effect of promoting urine discharge and in-vivo hypoglycemic activity, and compounds with equal or better in-vivo hypoglycemic activity than that of dapagliflozin are screened out, and can be used for the prevention or treatment of diabetes.
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Paragraph 0101-0104
(2017/07/12)
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- A stable and porous iridium(III)-porphyrin metal-organic framework: Synthesis, structure and catalysis
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Self-assembly of a new metalloporphyrin tetracarboxylic ligand Ir(TCPP)Cl (TCPP = tetrakis(4-carboxyphenyl)porphyrin) with ZrCl4 in the presence of benzoic acid leads to the formation of a three-dimensional (3D) iridium(III)-porphyrin metal-organic framework (Ir-PMOF) with the formula of [(Zr6(μ3-O)8(OH)2(H2O)10)2(Ir(TCPP)Cl)3]·solvents (Ir-PMOF-1(Zr)), which possesses square-shaped channels of 1.9 × 1.9 nm2 (atom-to-atom distances across opposite Ir metal atoms) in three orthogonal directions as disclosed by the single-crystal X-ray diffraction analysis. Ir-PMOF-1(Zr) represents the first MOF bearing a self-supporting iridium-porphyrin catalytic framework, featuring high porosity and stability. The catalytic tests disclose that the activated Ir-PMOF-1(Zr) can promote O-H insertion with a turnover frequency (TOF) up to 4260 h-1. Ir-PMOF-1(Zr) can be recycled and reused for 10 runs without significant loss of catalytic activity, and the total turnover number (TON) for O-H insertion after 10 successive runs reaches 875.
- Cui, Hao,Wang, Yingxia,Wang, Yanhu,Fan, Yan-Zhong,Zhang, Li,Su, Cheng-Yong
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p. 2203 - 2209
(2016/03/30)
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- DOPAMINE D2 RECEPTOR LIGANDS
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The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0- arrestin pathway and/or on the cAMP pathway.
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Page/Page column 143; 161; 162
(2016/07/05)
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- Dibenzo-azepine-dione anti-tumor compounds and preparation method thereof
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The invention provides dibenzo-azepine-dione anti-tumor compounds and a preparation method thereof, belongs to the technical field of medicines and particularly relates to compounds with specific chemical structures with anti-tumor activity. General formulae of the compounds include a general formula I, a general formula II, a general formula III and a general formula IV. The invention further provides an application of the compounds in anti-tumor and the preparation method. Tests of various tumor cell lines such as human lung cancer cells and human gastric carcinoma cells prove that the compounds have the tumor activity inhibition effect. The raw materials of the compounds are easily available, the preparation method is simple, and experiments prove that the compounds have good anti-cancer effect and have good application prospect in the field of design, research and development of anti-tumor drugs.
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Paragraph 0120; 0121
(2016/10/07)
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- Synthesis and properties of coumarin derivatives and their terbium complexes
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A series of coumarin derivatives obtained from salicylaldehyde and phenol were synthesized. Their corresponding terbium complexes were prepared and characterized by elemental analysis, EDTA titrations, molar conductivity, UVvis spectra, IR spectra, and thermal analysis. The luminescent properties and electrochemical properties of the terbium complexes were also investigated. The results showed that all the terbium complexes exhibited characteristic emissions of terbium ions. The introduction of electron-donating groups can improve the luminescent properties, decrease the HOMO and LUMO energy levels of the terbium complex, while electron-withdrawing groups can weaken the luminescent properties, and increase the HOMO and LUMO energy levels of terbium complex.
- Meng, Defen,Xu, De,Li, Dong,Dai, Ming,Li, Guizhi,Guo, Dongcai
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p. 5269 - 5280
(2016/06/01)
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- Formononetin derivatives and preparation methods and medical application thereof
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The invention relates to the field of pharmaceutical chemistry, and relates to formononetin derivatives and preparation methods and medical application thereof, in particular to formononetin derivatives with the general formula as shown in (I), preparation methods thereof, pharmaceutical compositions containing the compounds and medical application of the derivatives and the pharmaceutical compositions, particularly, application of the derivatives and the pharmaceutical compositions serving as drugs for preventing or treating hyperlipidaemia or obesity or type-II diabetes. Please see the formula in the description.
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Paragraph 0051; 0052; 0053; 0057; 0058; 0059
(2017/04/29)
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- Novel hybrid-pyrrole derivatives: Their synthesis, antitubercular evaluation and docking studies
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Using novel hybrid molecules for the treatment of tuberculosis is one of the latest approaches. Keeping this concept in mind, thirty two hybrid compounds were synthesized, with pyrrole as one of the moieties, clubbed to coumarin, ibuprofen and isoniazid. The compounds were evaluated against Mycobacterium tuberculosis H37Rv strain. Compounds 7e and 8e exhibited MIC of 3.7 and 5.10 μg mL-1 and growth inhibition of 95% and 92%, respectively. These compounds were also active against single drug resistant bacterial strains. The compounds were devoid of cytotoxicity when tested against Vero African green monkey kidney cell line. Docking study was carried out on enoyl acyl carrier protein enzyme to provide some understanding into the mechanism of action of these compounds.
- Saha, Rikta,Alam, Md. Mumtaz,Akhter, Mymoona
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p. 12807 - 12820
(2015/02/19)
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- Synthesis, Characterization and Properties of Novel Coumarin Derivatives and Their Europium Complexes
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Seven novel coumarin derivatives derived from salicylaldehyde and phenol were synthesized and characterized by 1H NMR and 13C NMR spectra, mass spectra, infrared spectra and elemental analysis. Their corresponding Eu(III) complexes having general formula EuL1-7(NO3)3·2H2O were successfully prepared and characterized by elemental analysis, EDTA titrimetric, molar conductivity, UV-Vis, FT-IR and thermal performance studies. The luminescence properties, fluorescence quantum yields and the electrochemical properties of the title complexes were investigated. The results showed that the title complexes exhibited characteristic emissions of europium ions and possessed relatively good fluorescence quantum yields. The luminescence intensity of the complex with bromine-substituted group is the strongest among all the title complexes. The introduction of electron-withdrawing groups can increase the luminescence properties and fluorescence quantum yields, decrease the HOMO and LUMO energy levels of the title europium complexes, but electron-withdrawing group conversely. And these title complexes may possibly be useful for studying in luminescent materials field.
- Yan, Dong,Li, Dong,Cheng, Guang,Yang, Zehui,Shi, Ling,Guo, Dongcai
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p. 849 - 859
(2015/08/24)
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- Synthesis and Characterization of 5-Hydroxy-2-(2-phenylethyl)chromone (5-HPEC) and Its Analogues as Non-nitrogenous 5-HT2B Ligands
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The involvement of the neurotransmitter serotonin (5-HT) in numerous physiological functions is often attributed to the diversity of receptors with which it interacts. Ligands targeting serotonin receptor 2B (5-HT2B) have received renewed interest for their potential to help understand the role of 5-HT2B in migraines, drug abuse, neurodegenerative diseases, and irritable bowel syndrome. To date, most of the ligands targeting 5-HT2B have been nitrogen-containing compounds. The natural product 5-hydroxy-2-(2-phenylethyl)chromone (5-HPEC, 5) has been shown previously to act as a non-nitrogenous antagonist for the 5-HT2B receptor (pKi = 5.6). This report describes further progress on the study of the structure-activity relationship of both naturally occurring and synthetic compounds bearing the 2-(2-phenylethyl)chromone scaffold at the 5-HT2B receptor. The inhibitory activity of the newly synthesized compounds (at 10 μM) was tested against each of the 5-HT2 receptors. Following this assay, the binding affinity and antagonism of the most promising compounds were then evaluated at 5-HT2B. Among all the analogues, 5-hydroxy-2-(2-phenylpropyl)chromone (5-HPPC, 22h) emerged as a new lead compound, showing a 10-fold improvement in affinity (pKi = 6.6) over 5-HPEC with reasonable antagonist properties at 5-HT2B. Additionally, ligand docking studies have identified a putative binding pocket for 5-HPPC and have helped understand its improved affinity. (Figure Presented).
- Williams, Dwight A.,Zaidi, Saheem A.,Zhang, Yan
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p. 1859 - 1867
(2015/09/08)
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- 2-SUBSTITUTED-5-HYDROXY-4H-CHROMEN-4-ONES AS NOVEL LIGANDS FOR THE SEROTONIN RECEPTOR 2B (5-HT2B)
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A family of compounds which function as selective ligands for the serotonin receptor 2B (5-HT2B) is identified. Some of the compounds are synthetic non-natural ligands which have a relatively strong interaction with 5-HT2B compared to naturally occurring compounds (some of which are identified for the first time herein as ligands for 5-HT2B). Because the compounds, both naturally occurring and synthetically produced, function as ligands for 5-HT2B they will have application in, for example, the treatment and/or prevention of nervous system disorders such as Alzheimer's disease.
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Page/Page column 32; 33
(2015/09/22)
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- Synthesis, antiproliferative activity, and molecular docking studies of curcumin analogues bearing pyrazole ring
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Several curcumin analogues bearing pyrazole were synthesized and characterized by IR, NMR, and mass spectral data. There were four tested compounds among 11 synthesized compounds, which were evaluated for antiproliferative activity and showed significant activity in both one-dose and five-dose assays. The antiproliferative effects were tested on a panel of 60 cell lines, according to the National Cancer Institute screening protocol. The most active compounds among the series were 3,5-bis(4-hydroxy-3-methylstyryl)-1H-pyrazole-1-carboxamide (3k) which showed mean percent growth inhibition of 116.09 in one-dose assay at 10 μM, and GI50 values were ranging between 0.0912 and 2.36 μM in five-dose assay. The best results were recorded on the leukaemia cell lines with value ranging from 0.0912 to 0.365 μM. All the tested compounds showed broad-spectrum antiproliferative activity over different cancer cell lines. When compared with the standard drug paclitaxel, the compound 3k showed superior activity on nearly 42 cell lines. The molecular docking study was performed to explore the binding interaction of these curcumin analogues with the active site of EGFR tyrosine kinase (EGFR-TK). The hydroxyl group of both phenyl rings was important for the rein-geminated hydrogen bonding by either side chain or backbone with the active site of EGFR-TK. Graphical Abstract: Four curcumin analogues were evaluated for their antiproliferative activity and showed promising results. The molecular docking studies showed that all the compounds (3a-k) were well accommodated in the EGFR tyrosine kinase.[Figure not available: see fulltext.]
- Ahsan, Mohamed Jawed,Choudhary, Kavita,Jadav, Surender Singh,Yasmin, Sabina,Ansari, Md. Yousuf,Sreenivasulu, Reddymasu
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p. 4166 - 4180
(2015/11/02)
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- Synthesis and luminescence properties of pyrazolone derivatives and their terbium complexes
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Seven novel pyrazolone derivatives were synthesized and characterized by 1H NMR and 13C NMR spectra, mass spectra, infrared spectra and elemental analysis. Their terbium complexes were prepared and characterized by elemental analysis, EDTA titrimetric analysis, UV/vis spectra, infrared spectra and molar conductivity, as well as thermal analysis. The fluorescence properties and fluorescence quantum yields of the complexes were investigated at room temperature. The results indicated that pyrazolone derivatives had good energy-transfer efficiency for the terbium ion. All the terbium complexes emitted green fluorescence characteristic of terbium ions, possessed strong fluorescence intensity, and showed relatively high fluorescence quantum yields. Cyclic voltammograms of the terbium complexes were studied and the highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) energy levels of these complexes were estimated.
- Xiao, Haihua,Jiang, Xi,Li, Dong,Wu, Limin,Zhang, Wu,Guo, Dongcai
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p. 677 - 685
(2015/12/04)
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- Radical decarboxylative fluorination of aryloxyacetic acids using N-fluorobenzenesulfonimide and a photosensitizer
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Fluorinated methoxy arenes are emerging as important motifs in both agrochemicals and pharmaceuticals. A novel technique for the synthesis of monofluoromethoxy arenes through the direct fluorodecarboxylation of carboxylic acids was developed that uses photosensitizers and N-fluorobenzenesulfonimide (NFSI). Utilization of the oxidatively mild fluorine transfer agent NFSI enabled the synthesis of fluoromethyl ethers that were previously inaccessible with decarboxylative fluorinations performed with Selectfluor. Mechanistic studies are consistent with the photosensitizer effecting oxidation of the aryloxyacetic acid.
- Leung, Joe C. T.,Sammis, Glenn M.
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supporting information
p. 2197 - 2204
(2015/04/14)
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- Bis azide-triphenylphosphine as a reagent for esterification at room temperature
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Modified Staudinger reaction is a well-established reaction for the amide synthesis from organic azides and carboxylic acids in the presence of phosphorous reagents. In contrary to this, it is notable that bis azide in the presence of triethylphosphite or trimethylphosphite does not afford the expected bis amides but affords the ethyl or methyl esters of the carboxylic acids respectively. This serendipitous observation when further investigated results in the discovery of bis azide-triphenylphosphine as an efficient reagent for esterification at room temperature.
- Dinesh, Murugan,Archana, Sivasubramaniyan,Ranganathan, Raja,Sathishkumar, Murugan,Ponnuswamy, Alagusundaram
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supporting information
p. 6975 - 6979
(2015/11/27)
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- Aggregation behaviours and bactericidal activities of novel cationic surfactants functionalized with amides and ether groups
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A series of novel cationic surfactants, N-alkylcaramoylmethyl-N-[2-(2-phenoxyacetamido)-ethyl]-N,N-dimethylammonium chloride, were synthesized and their chemical structures were characterized using 1H-NMR, 13C-NMR, ESI-MS and FT-IR. Their aggregation behaviours in aqueous solution were systematically investigated by surface tension and electrical conductivity methods. It was found that the surfactants have higher surface activity compared with a similar structural surfactant. A series of thermodynamic parameters of aggregation indicate that the aggregation is entropy-driven at the investigated temperatures. In addition, they possess excellent bactericidal activities against the selected strains. This journal is
- Cao, Guangzhou,Guo, Xiangfeng,Jia, Lihua,Tian, Xuhua
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p. 27197 - 27204
(2015/03/30)
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- Synthesis and biological evaluation of isoflavone amide derivatives with antihyperlipidemic and preadipocyte antiproliferative activities
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A series of isoflavone amides were designed with isoflavone in place of the scaffold of 2-arylbenzoxazole as cholesterol ester transfer protein (CETP) inhibitors. Twelve new compounds were synthesized, and their inhibitory activities of CETP and preadipocyte proliferation were assayed. The hypolipidemic potency of the most effective compound HY-2c was further tested in vivo by hamster. The results indicate that HY-2c exhibited favorable antihyperlipidemic and preadipocyte antiproliferative activities.
- Wang, Wenbin,He, Yi,Xu, Pei,You, Qidong,Xiao, Hong,Xiang, Hua
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p. 4428 - 4433
(2015/08/03)
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- Design, Synthesis and in vivo Evaluation of Novel C-Aryl Glucosides as Potent Sodium-Dependent Glucose Cotransporters Inhibitors for the Treatment of Diabetes
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A series of novel C-aryl glucosides with substituents at the 3′-position or cyclization at 3′, 4′-positions of the distal aryl ring were designed and synthesized, which might decrease the oxidative metabolism of dapagliflozin. Preliminary evaluation for hypoglycemic effect and the risk of hypoglycemia were carried out both in normal and in streptozotocin-induced diabetic mice. Among the synthesized compounds, compound 19a exerted potency-similarity with dapagliflozin and triggered the hypoglycemic effect in a dose-dependent manner. Besides, compound 19a, even at the high dose of 10 mg/kg, revealed a low risk of hypoglycemia. In further studies, 19a exhibited sustained antihyperglycemic effect without particular side-effects in 30-day chronic diabetic mice studies. Moreover, histological changes in the pancreas of diabetic mice indicated 19a might protect pancreatic β-cell from apoptosis by reducing the damage of glucotoxicity. All of these results demonstrated that compound 19a, with excellent in vivo pharmacological activity and safety profile, was considered to be a promising drug candidate for the treatment of diabetes mellitus.
- Li, Zheng,Wang, Xuekun,Xu, Xue,Qiu, Qianqian,Jiao, Lei,Huang, Wenlong,Qian, Hai
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p. 764 - 775
(2015/03/30)
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- Design, synthesis, molecular docking and 3D-QSAR studies of potent inhibitors of enoyl-acyl carrier protein reductase as potential antimycobacterial agents
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In order to develop a lead antimycobacterium tuberculosis compound, a series of 52, novel pyrrole hydrazine derivatives have been synthesized and screened which target the essential enoyl-ACP reductase. The binding mode of the compounds at the active site of enoyl-ACP reductase was explored using surflex-docking method. The binding model suggests one or two hydrogen bonding interactions between pyrrole hydrazones and InhA enzyme. Highly active compound 5r (MIC 0.2 μg/mL) showed hydrogen bonding interactions with Tyr158 and NAD+ in the same manner as those of ligands PT70 and triclosan. The CoMFA and CoMSIA models generated with database alignment were the best in terms of overall statistics. The predictive ability of the CoMFA and CoMSIA models was determined using a test set of 13 compounds, which gave predictive correlation coefficients (rpred2) of 0.896 and 0.930, respectively.
- More, Uttam A.,Joshi, Shrinivas D.,Aminabhavi, Tejraj M.,Gadad, Andanappa K.,Nadagouda, Mallikarjuna N.,Kulkarni, Venkatrao H.
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p. 199 - 218
(2014/01/06)
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- Anthelmintic evaluation of some novel synthesized 1,2,4-triazole moiety clubbed with benzimidazole ring
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A series of N-[3-{(1H-benzo[d]imidazol-2-ylthio) methyl}-5-mercapto-4H-1,2, 4-triazol-4-yl]-2-substituted phenoxy acetamide 6(a-g) were synthesized by the mixture of the compound of potassium 2-(2-(1H-benzo[d]imidazol-2-ylthio) acetyl) hydrazinecarbodithioate (4) and arytoxy acid hydrazide (5) in presence of hydrochloric acid. The predicted structures of the synthesized compounds were confirmed by different spectral analysis studies. The title compounds 6(a-g) were screened for anthelmintic activity against Pheretima posthumous. The entire compounds were exhibited good anthelmintic activity when compared with standard drugs such as Albendazole and Piperazine.
- Kumar, P. Sudhir,Sahoo
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p. 211 - 217
(2014/06/23)
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- ANTIINFLAMMATORY AND ANTITUMOR 2-OXOTHIAZOLES AND 2-OXOTHIOPHENES COMPOUNDS
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A compound of formula (I) wherein X is O, C O or S; Y is N or CH; R2 and R4 are each independently H, -(CH2)pCOOH, -(CH2)pCON(R5)2 or - (CH2)pCOOC 1-6alkyI; or R2 and R4 together form a 6-membered phenyl ring fused to the five membered ring; each R1 is independently selected from H, halo (e.g. fluoro or chloro), C6-10aryl, C7-12arylalkyl, C2-12alkenyl; OC1-2 alkyl, OC2-12 aikenyl or a C1-12 alkyl group; each R5 is H or C1-6 alkyl; each p is 0 to 3; n is 1 to 4; or a salt, ester, solvate, N-oxide, or prodrug thereof, e.g. a salt thereof.
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Page/Page column 54
(2014/08/19)
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- Inhibition of group IVA cytosolic phospholipase A2by thiazolyl ketones in vitro, ex vivo, and in vivo
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Group IVA cytosolic phospholipase A2(GIVA cPLA2) is the rate-limiting provider of pro-inflammatory mediators in many tissues and is thus an attractive target for the development of novel anti-inflammatory agents. In this work, we present the synthesis of new thiazolyl ketones and the study of their activities in vitro, in cells, and in vivo. Within this series of compounds, methyl 2-(2-(4-octylphenoxy)acetyl)thiazole-4-carboxylate (GK470) was found to be the most potent inhibitor of GIVA cPLA2, exhibiting an XI(50) value of 0.011 mole fraction in a mixed micelle assay and an IC50of 300 nM in a vesicle assay. In a cellular assay using SW982 fibroblast-like synoviocytes, it suppressed the release of arachidonic acid with an IC50value of 0.6 μM. In a prophylactic collagen-induced arthritis model, it exhibited an anti-inflammatory effect comparable to the reference drug methotrexate, whereas in a therapeutic model, it showed results comparable to those of the reference drug Enbrel. In both models, it significantly reduced plasma PGE2levels.
- Kokotos, George,Feuerherm, Astrid J.,Barbayianni, Efrosini,Shah, Ishita,S?ther, Mari,Magrioti, Victoria,Nguyen, Thuy,Constantinou-Kokotou, Violetta,Dennis, Edward A.,Johansen, Berit
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p. 7523 - 7535
(2015/01/08)
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- Unprecedented organocatalytic reduction of lignin model compounds to phenols and primary alcohols using hydrosilanes
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The first metal-free reduction of lignin model compounds is described. Using inexpensive Et3SiH, PMHS and TMDS hydrosilanes as reductants, α-O-4 and β-O-4 linkages are reduced to primary alcohols and phenols under mild conditions using B(C6F5)3 as an efficient catalyst. The Royal Society of Chemistry.
- Feghali, Elias,Cantat, Thibault
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supporting information
p. 862 - 865
(2014/01/06)
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