- Synthesis, characterization, antidepressant and antioxidant activity of novel piperamides bearing piperidine and piperazine analogues
-
A series of piperamide derivatives (8a-j) was synthesized with various substituted piperidine and piperazine compounds. The prepared compounds were evaluated for antibacterial activity against gram-positive and gram-negative bacteria and antifungal activity by disc diffusion method. The antioxidant activity of the compounds was evaluated by DPPH and superoxide radical scavenging method and antidepressant activity using forced swim and tail suspension behavioral despair tests in mice. The compounds 8a, 8b and 8c were investigated for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory property. Some of the test compounds were active in forced swim test (FST) and tail suspension test (TST). Compounds 8a and 8b showed a significant effect, when compared to standard drug, clorgyline.
- Prashanth,Revanasiddappa, Hosakere D.,Lokanatha Rai,Veeresh
-
-
Read Online
- 4-Alkyliden-azetidinones modified with plant derived polyphenols: Antibacterial and antioxidant properties
-
Antimicrobial resistance is one of the major and growing concerns in hospital- and community acquired infections, and new antimicrobial agents are therefore urgently required. It was reported that oxidative stress could contribute to the selection of resistant bacterial strains, since reactive oxygen species (ROS) revealed to be an essential driving force. In the present work 4-alkylidene-azetidinones, a new class of antibacterial agents, were functionalized with phytochemical polyphenolic acids such as protocatechuic, piperonyl, caffeic, ferulic, or sinapic acids and investigated as dual target antibacterial-antioxidant compounds. The best candidates showed good activities against multidrug resistant clinical isolates of MRSA (MICs 2–8 μg/mL). Among the new compounds, two revealed the best antioxidant capacity with TEAC-DPPH and TEAC-ABTS being significantly more active than Trolox.
- Giacomini, Daria,Musumeci, Rosario,Galletti, Paola,Martelli, Giulia,Assennato, Lorenzo,Sacchetti, Gianni,Guerrini, Alessandra,Calaresu, Enrico,Martinelli, Marianna,Cocuzza, Clementina
-
-
Read Online
- Quorum sensing and nf-κb inhibition of synthetic coumaperine derivatives from piper nigrum
-
Bacterial communication, termed Quorum Sensing (QS), is a promising target for virulence attenuation and the treatment of bacterial infections. Infections cause inflammation, a process regulated by a number of cellular factors, including the transcription Nuclear Factor kappa B (NF-κB); this factor is found to be upregulated in many inflammatory diseases, including those induced by bacterial infection. In this study, we tested 32 synthetic derivatives of coumaperine (CP), a known natural compound found in pepper (Piper nigrum), for Quorum Sensing Inhibition (QSI) and NF-κB inhibitory activities. Of the compounds tested, seven were found to have high QSI activity, three inhibited bacterial growth and five inhibited NF-κB. In addition, some of the CP compounds were active in more than one test. For example, compounds CP-286, CP-215 and CP-158 were not cytotoxic, inhibited NF-κB activation and QS but did not show antibacterial activity. CP-154 inhibited QS, decreased NF-κB activation and inhibited bacterial growth. Our results indicate that these synthetic molecules may provide a basis for further development of novel therapeutic agents against bacterial infections.
- Baruch, Yifat,Gopas, Jacob,Kadosh, Yael,Kumar, Rajendran Saravana,Kushmaro, Ariel,Muthuraman, Subramani,Yaniv, Karin
-
supporting information
(2021/05/28)
-
- Simplified Derivatives of Dibenzylbutyrolactone Lignans from Hydrocotyle bonariensis as Antitrypanosomal Candidates
-
The search for the pharmacophore of a bioactive compound, crucial for drug discovery studies, involves the adequate arrangement of different atoms in the molecule. As part of a continuous work aiming discovery of new drug candidates against the protozoan parasite Trypanosoma cruzi, the hexane extract of Hydrocotyle bonariensis was subjected to a bioactivity-guided fractionation to afford two chemically related dibenzylbutyrolactone lignans – hinokinin (1) and hibalactone (2). Compounds 1 and 2 showed activity against trypomastigote with EC50 values of 17.0 and 69.4 μM, respectively. Compound 1 was also active against the clinically relevant form of the parasite, amastigotes, displaying an EC50 value of 34.4 μM. The structure-activity relationship (SAR) indicated that the absence of the double bond at C-7 is a crucial feature for the increment of the antiparasitic activity. The lethal action of the most potent compound 1 was investigated in the trypomastigotes. The fluorescent-based assay with SYTOX Green demonstrated a significant alteration of the plasma membrane permeability of the parasite. Additionally, compound 1 demonstrated no significant hemolytic activity in mice erythrocytes at 200 μM. To search the pharmacophore, three different simplified compounds – 3,4-methylenedioxydihydrocinnamic acid (3), 3,4-methylenedioxydihydrocinnamic alcohol (4) and 3,4-methylenedioxycinnamic acid (5) – were prepared and tested against T. cruzi. These derivatives displayed EC50 values of 37.2 (3), 25.8 (4) and 73.5 (5) μM against trypomastigotes, and 41.3 (3) and 48.2 (4) μM against amastigotes, whereas compound 5 was inactive. Except for compound 2, which resulted in a CC50 value of 114.5 μM, all compounds showed no mammalian cytotoxicity at 200 μM. An in silico ADMET study was performed and predicted values demonstrated an acceptable drug-likeness profile for compounds 1–5. Despite the minor reduction in the potency, the simplified derivatives retained the antitrypanosomal activity against the intracellular amastigotes, even with 95 % reduction of their molecular weight. Additionally, in silico studies suggested them as more soluble compounds, making these simplified structures promising scaffolds for optimization studies in Chagas disease.
- Souza, Dalete Christine S.,Costa-Silva, Thais A.,Morais, Thiago R.,Brito, Juliana R.,Ferreira, Edgard A.,Antar, Guilherme M.,Sartorelli, Patricia,Tempone, Andre G.,Lago, Jo?o Henrique G.
-
-
- Dual Nickel/Ruthenium Strategy for Photoinduced Decarboxylative Cross-Coupling of α,β-Unsaturated Carboxylic Acids with Cycloketone Oxime Esters
-
Herein, a dual nickel/ruthenium strategy is developed for photoinduced decarboxylative cross-coupling between α,β-unsaturated carboxylic acids and cycloketone oxime esters. The reaction mechanism is distinct from previous photoinduced decarboxylation of α,β-unsaturated carboxylic acids. This reaction might proceed through a nickelacyclopropane intermediate. The C(sp2)-C(sp3) bond constructed by the aforementioned reaction provides an efficient approach to obtaining various cyanoalkyl alkenes, which are synthetically valuable organic skeletons in organic and medicinal chemistry, under mild reaction conditions. The protocol tolerates many critical functional groups and provides a route for the modification of complex organic molecules.
- Gao, Ang,Jiang, Run-Chuang,Liu, Chuang-Chuang,Liu, Qi-Le,Lu, Xiao-Yu,Xia, Ze-Jie
-
supporting information
p. 8829 - 8842
(2021/06/30)
-
- Identification of novel functionalized carbohydrazonamides designed as chagas disease drug candidates
-
Background: Although several research efforts have been made worldwide to discover novel drug candidates for the treatment of Chagas disease, the nitroimidazole drug benznidazol remains the only therapeutic alternative in the control of this disease. However, this drug presents reduced efficacy in the chronic form of the disease and limited safety after long periods of admini-stration, making it necessary to search for new, more potent and safe prototypes. Objective: We described herein the synthesis and the trypanocidalaction of new functionalized carbohydrazonamides (2-10) against trypomastigote forms of Trypanosoma cruzi. Methods: These compounds were designed through the application of molecular hybridization concept between two potent anti-T. cruzi prototypes, the nitroimidazole derivative megazol (1) and the cinnamyl N-acylhydrazone derivative (14) which have been shown to be twice as potent in vitro as benznidazole. Results: The most active compounds were the (Z)-N'-((E)-3-(4-nitrophenyl)-acryloyl)-1-methyl-5-nitro-1H-imidazol-2-carbohydrazonamide (6) (IC50 =9.50 μM) and the (Z)-N'-((E)-3-(4-hydroxyphe-nyl)-acryloyl)-1-methyl-5-nitro-1H-imidazol-2-carbohydrazonamide (8) (IC50 =12.85 μM), which were almost equipotent to benznidazole (IC50 =10.26 μM) used as standard drug. The removal of the amine group attached to the imine subunit in the corresponding N-acylhydrazone derivatives (11-13) resulted in less potent or inactive compounds. The para-hydroxyphenyl derivative (8) presented also a good selectivity index (SI = 32.94) when tested against mammalian cells from Swiss mice. Conclusion: The promising trypanocidal profile of new carbohydrazonamide derivatives (6) and (8) was characterized. These compounds have proved to be a good starting point for the design of more effective trypanocidal drug candidates.
- Do Nascimento, Mayara S. S.,Camara, Vitória R. F.,da Costa, Juliana S.,Barbosa, Juliana M. C.,Lins, Alessandra S. M.,Salom?o, Kelly,de Castro, Solange L.,Carvalho, Samir A.,da Silva, Edson F.,Fraga, Carlos A. M.
-
p. 774 - 783
(2020/08/19)
-
- Identification and optimization of piperine analogues as neuroprotective agents for the treatment of Parkinson's disease via the activation of Nrf2/keap1 pathway
-
Parkinson's disease (PD) is a slowly progressive and complex neurodegenerative disorder. Up to date, there are no approved drugs that could slow or reverse the neurodegenerative process of PD. Here, we reported the synthesis of series of piperine analogues and the evaluation of their neuroprotective effects against hydrogen peroxide (H2O2) induced damage in the neuron-like PC12 cells. Among these analogues, 3b exhibited the most potent protection effect and its underlying mechanism was further investigated. Further results indicated that the ROS scavenging and cytoprotection effect of 3b might be related to the Nrf2 activation and upregulation of related phase II antioxidant enzymes, such as HO-1 and NQO1. In in vivo study, oral administration (100 mg/kg) of 3b significantly attenuated PD-associated behavioral deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and protected tyrosine hydroxylase-immunopositive dopaminergic neurons. Our results provided evidence that 3b might be a promising candidate for Parkinson's disease treatment.
- Cai, Xiaoying,Chen, Lijuan,Hong, Feng,Kuang, Shuang,Li, Yan,Ma, Xu,Qi, Wenyan,Shi, Mingsong,Wang, Lun,Xu, Ruiling,Xue, Linlin,Ye, Haoyu,Zhang, Ruijia
-
-
- Synthesis and antimicrobial evaluation of piperic acid amides and their lower homologues
-
Seven piperic acid amides along with their lower homologs (12) were synthesized using HATU-DIPEA coupling reagent. All the synthesized derivatives were evaluated for their antibacterial activities against Staphylococcus aureus, Pseudomonas aeruginosa, and vancomycin-resistant P. aeruginosa. They were found to be more active on P. aeruginosa than on S. aureus. However, they did not exhibit potent activity on Vancomycin resistant P. aeruginosa. Among the tested compounds, methylenedioxycinnamic acid amide of anthranilic acid (MDCA-AA, 2a) was found to be most active against S. aureus with MIC of 3.125 μg/ml. The PAS and INH amides of piperic acid were screened against Mycobacterium tuberculosis H37Ra strain. They were found to be most active among all the tested compounds but were found to be less active than the standard drug, isoniazid.
- Achanta, Prabhakar S.,Raj, Sneha,Horam, Soyar,Arockiaraj, Jesu,Bobbala, Ravi Kumar,Akkinepally, Raghuram Rao,Pasupuleti, Mukesh,Achanta, Appa Rao V. N.
-
p. 366 - 373
(2019/12/12)
-
- Piperine derivative as well as preparation method and application thereof
-
The invention provides a piperine derivative as well as a preparation method and an application thereof. The piperine derivative is a compound shown as a formula (I), or a salt thereof, or a stereoisomer thereof, or a hydrate thereof. The compound provided by the invention can effectively protect nerve cells and improve the survival rate of the nerve cells, so that the compound provided by the invention can effectively treat neurodegenerative diseases and can be used for preparing medicines for treating the neurodegenerative diseases.
- -
-
Paragraph 0255; 0257-0259
(2020/05/08)
-
- Mild, Metal-Free and Protection-Free Transamidation of N-Acyl-2-piperidones to Amino Acids, Amino Alcohols and Aliphatic Amines and Esterification of N-Acyl-2-piperidones
-
Amides are indispensable building blocks of biological systems, pharmaceuticals, and materials. We report a highly selective method for the synthesis of amides via transamidation process. Transamidation of N-acyl-2-piperidones with a broad range of amines is demonstrated under exceedingly mild and metal-free reaction condition that relies on the amide bond twist to weaken the amidic resonance. Transamidation proceeds under the neat condition at room temperature, in short reaction times (30–90 min) with good yields. Considerable variation is tolerated with both amine and imide substrates. Of note, amines bearing carboxylic acids (glycine and serine) and hydroxyl groups (dopamine, tyramine, etc.) are well tolerated which are otherwise problematic under the metal-catalyzed protocol. Our current method is applicable for transamidation of both alkyl and aryl-N-acyl-2-piperidones. The practical value of the method is highlighted by the synthesis of four natural product amide alkaloids in high yields under mild reaction conditions. In the absence of nucleophilic amines, N-acyl-2-piperidones undergoes esterification with EtOH at elevated temperature. Single crystal X-ray analysis of an N-acyl-2-piperidone shows amide bond twist, τ = –20.39° and pyramidalization, χN = –11.73°. This weakens the amidic conjugation and might be the factor controlling the reactivity and selectivity of these imides. We envision that the N-acyl-2-piperidone scaffold would be useful in the synthesis of pharmaceuticals and materials.
- Subramani, Muthuraman,Rajendran, Saravana Kumar
-
supporting information
p. 3677 - 3686
(2019/06/08)
-
- Design, synthesis and identification of novel coumaperine derivatives for inhibition of human 5-LOX: Antioxidant, pseudoperoxidase and docking studies
-
5-Lipoxygenase (5-LOX) is a key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes, leading to asthma. Developing potent 5-LOX inhibitors especially, natural product based ones, are highly attractive. Coumaperine, a natural product found in white pepper and its derivatives were herein developed as 5-LOX inhibitors. We have synthesized twenty four derivatives, characterized and evaluated their 5-LOX inhibition potential. Coumaperine derivatives substituted with multiple hydroxy and multiple methoxy groups exhibited best 5-LOX inhibition. CP-209, a catechol type dihydroxyl derivative and CP-262-F2, a vicinal trihydroxyl derivative exhibited, 82.7% and 82.5% inhibition of 5-LOX respectively at 20 μM. Their IC50 values are 2.1 ± 0.2 μM and 2.3 ± 0.2 μM respectively, and are comparable to zileuton, IC50 = 1.4 ± 0.2 μM. CP-155, a methylenedioxy derivative (a natural product) and CP-194, a 2,4,6-trimethoxy derivative showed 76.0% and 77.1% inhibition of 5-LOX respectively at 20 μM. Antioxidant study revealed that CP-209 and 262-F2 (at 20 μM) scavenged DPPH radical by 76.8% and 71.3% respectively. On the other hand, CP-155 and 194 showed very poor DPPH radical scavenging activity. Pseudo peroxidase assay confirmed that the mode of action of CP-209 and 262-F2 were by redox process, similar to zileuton, affecting the oxidation state of the metal ion in the enzyme. On the contrary, CP-155 and 194 probably act through some other mechanism which does not involve the disruption of the oxidation state of the metal in the enzyme. Molecular docking of CP-155 and 194 to the active site of 5-LOX and binding energy calculation suggested that they are non-competitive inhibitors. The In-Silico ADME/TOX analysis shows the active compounds (CP-155, 194, 209 and 262-F2) are with good drug likeliness and reduced toxicity compared to existing drug. These studies indicate that there is a great potential for coumaperine derivatives to be developed as anti-inflammatory drug.
- Muthuraman, Subramani,Sinha, Shweta,Vasavi,Waidha, Kamran Manzoor,Basu, Biswarup,Munussami, Punnagai,Balamurali,Doble, Mukesh,Saravana Kumar, Rajendran
-
supporting information
p. 604 - 619
(2019/01/14)
-
- Synthesis and biological evaluation of 2,2-dimethylbenzopyran derivatives as potent neuroprotection agents
-
The development of novel neuroprotection agents is of great significance for the treatment of ischemic stroke. In this study, a series of compounds comprising 2,2-dimethylbenzopyran groups and cinnamic acid groups have been synthesized. Preferential combination principles and bioisostere that improved the neuroprotective effect of the compounds were identified for this series via biological activity assay in vitro. Meanwhile, a functional reversal group of the acrylamide amide resulted in the most active compounds. Among them, BN-07 significantly improved the morphology of neurons and obviously increased cell survival rate of primary neurons induced by oxygen glucose deprivation (OGD), superior to clinically used anti-ischemic stroke drug edaravone (Eda). Overall, our findings may provide an alternative strategy for the design of novel anti-ischemic stroke agents with more potency than Eda.
- Du, Fangyu,Zhou, Qifan,Fu, Xiaoxiao,Shi, Yajie,Chen, Yuanguang,Fang, Wuhong,Yang, Jingyu,Chen, Guoliang
-
p. 2498 - 2508
(2019/02/01)
-
- Cyclotriol derivative and production method and application thereof
-
The invention discloses a cyclotriol derivative and a production method and application thereof. The cyclotriol derivative is of a structure as shown in a general formula I, wherein R1, R2 and R3 areOH or AcNH; R1=OH, and R2=R3=AcNH or R2=OH, and R1=R3=AcNH or R3=OH, and R1=R2=AcNH; * stands for R configuration or S configuration; and Ac stands for caffeoyl CAc or derivatives caffesulfonyl SAc and caffe(mono-methyl ester)phosphonyl PAc of the caffeoyl CAc. According to the production method of the cyclotriol derivative, conditions are mild, automatic and industrial production are easy to achieve, operation is simple, convenient and safe, and the obtained cyclotriol derivative can act on anti-respiratory syncytial virus F protein, has high anti-RSV activity, low cell toxicity and high stability, can be used for producing medicines for treating virus infection, and is especially used for producing medicines for treating respiratory syncytial virus infection.
- -
-
Paragraph 0138; 0139; 0144; 0145
(2019/09/13)
-
- Quinic acid derivative and preparation method and application thereof
-
The invention discloses a quinic acid derivative and a preparation method and application thereof. The quinic acid derivative has a structure represented by a formula I, wherein R1, R2 and R3 are OH or AcNH; R1 = OH, R2 = R3 = AcNH, or R2 = OH, R1 = R3 = AcNH, or R3 = OH, R1 = R2 = AcNH; * represents an R configuration or an S configuration; and Ac represents caffeoyl CAc or a derivative caffesulfonyl SAc, and coffee(mono-methyl ester)phosphonyl PAc. The quinic acid derivative has the advantages of mild preparation conditions, simple and safe operation, high product purity and relatively hightotal yield, and the obtained quinic acid derivative can be used for preparing medicaments for treating viral infections, especially for preparing medicaments for treating influenza virus, parainfluenza virus and respiratory syncytial virus infections.
- -
-
Paragraph 0138; 0139; 0144; 0145
(2019/10/01)
-
- Design, synthesis, trypanocidal activity, and studies on human albumin interaction of novel s-alkyl-1,2,4-triazoles
-
Chagas disease is a neglected tropical disease caused by the hemoflagellated parasite Trypanosoma cruzi (Kinetoplastida). The only available drug to treat chagasic patients in Brazil, the nitroheterocycle benznidazole, is effective solely during the acute phase of the infection. There is accordingly a need to develop new therapeutic tools for the treatment of Chagas disease. This work reports the synthesis, trypanocidal evaluation and human serum albumin (HSA) interactions of a novel series of 1,2,4-triazoles. The new derivatives were synthesized via microwave irradiation in good yields. Most compounds showed toxic effects against T. cruzi with low toxicity to host cells. Three S-alkylated-triazoles showed the best activity profile against amastigotes, with half maximal inhibitory concentration (IC50) values of 3.95 ± 1.41, 4.15 ± 0.92 and 3.61 ± 0.65 μmol L-1, respectively. The interaction between HSA and 3-[(1E,3E)-4-(1,3-benzodioxol-5-yl)buta-1,3-dien-1-yl]-5-(butylthio)-4-cyclohexyl-4,5-dihydro-1H-1,2,4-triazole was investigated using multiple spectroscopic techniques and molecular docking, revealing that serum albumin is a potential endogenous carrier to this compound in the human bloodstream.
- Franklim, Tatiany N.,Freire-De-Lima, Leonardo,Chaves, Otávio A.,LaRocque-De-Freitas, Isabel F.,da Silva-Trindade, Joana D.,Netto-Ferreira, José C.,Freire-De-Lima, Célio G.,Decoté-Ricardo, Debora,Previato, José O.,Mendon?a-Previato, Lucia,De Lima, Marco E.F.
-
p. 1378 - 1394
(2019/08/26)
-
- Structural optimization of caffeoyl salicylate scaffold as NO production inhibitors
-
Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxide (NO) in RAW264.7 cells induced by lipopolysaccharides (LPS) effectively, but also have high safety in in vitro cytotoxic test, which could be comparable with D104. Molecular docking study on the peroxisome proliferator-activated receptor γ (PPARγ) protein revealed that compounds B12 and B13 can follow the same binding mode with D104, and the carboxyl group of caffeoyl salicylate scaffold might play a key role in the interaction with protein target, which implied the carboxyl group should be retained in the further optimization.
- Yu, Pan,Xia, Chao-Jie,Li, Dong-Dong,Wang, Zhenzhong,Xiao, Wei,Zhao, Lin-Guo
-
p. 1006 - 1014
(2019/09/12)
-
- Pd-Catalyzed decarboxylative cross-coupling reactions of epoxides with α,β-unsaturated carboxylic acids
-
A Pd-catalyzed decarboxylative cross-coupling of α,β-unsaturated carboxylic acids with cyclic and acyclic epoxides has been developed. Both β-monosubstituted and β-disubstituted unsaturated carboxylic acids, as well as conjugated diene unsaturated carboxylic acids are suitable reaction substrates. Substituted homoallylic alcohols were obtained in moderate to good yields. The product was obtained as a mixture of diastereomers favoring the anti diastereomer of the cyclic epoxides. This work provides a method for the modification of complex organic molecules containing α,β-unsaturated carboxylic acids.
- Lu, Xiao-Yu,Li, Jin-Song,Wang, Shi-Qun,Zhu, Yu-Jing,Li, Yue-Ming,Yan, Lu-Yu,Li, Jia-Mei,Wang, Jin-Yu,Zhou, Hai-Pin,Ge, Xiu-Tao
-
supporting information
p. 11123 - 11126
(2019/09/20)
-
- Synthesis of Analogs of Trans-Fagaramide and Their Cytotoxic Activity
-
A series of 30 compounds were synthetized inspired by active trans-fagaramide structure skeleton. On this synthetic platform, 18 compounds were achieved via Knoevenagel condensation using maleic acid and piperonal, followed by peptide coupling with various amines, giving an average yield of 54%. Subsequently, nine compounds were obtained by palladium-mediated Heck coupling with an average yield of 79%. In addition, cytotoxic activity was evaluated against cardiomyoblast H9c2, breast adenocarcinoma MCF7, hepatocellular carcinoma HepG2, and glioblastoma U-87 cells. The results revealed two aryl halogen-substituted compounds moderately active against H9c2 and MCF7 with IC50 values > 50 μM. One functionalized coumarin showed inhibitory activity against H9c2 (IC50 > 50 μM). In contrast, p-aminophenyl-β-monosubstituted trans-fagaramide was found to inhibit MCF7 (IC50 > 50 μM) without showing toxicity against H9c2 cells.
- Tomas, Melissa Barrera,Shiao, Tze Chieh,Nguyen, Phuong Trang,Bourgault, Steve,Roy, René
-
p. 995 - 1004
(2018/02/22)
-
- Discovery of caffeic acid phenethyl ester derivatives as novel myeloid differentiation protein 2 inhibitors for treatment of acute lung injury
-
Myeloid differentiation protein 2 (MD2) is an essential molecule which recognizes lipopolysaccharide (LPS), leading to initiation of inflammation through the activation of Toll-like receptor 4 (TLR4) signaling. Caffeic acid phenethyl ester (CAPE) from propolis of honeybee hives could interfere interactions between LPS and the TLR4/MD2 complex, and thereby has promising anti-inflammatory properties. In this study, we designed and synthesized 48 CAPE derivatives and evaluated their anti-inflammatory activities in mouse primary peritoneal macrophages (MPMs) activated by LPS. The most active compound, 10s, was found to bind with MD2 with high affinity, which prevented formation of the LPS/MD2/TLR4 complex. The binding mode of 10s revealed that the major interactions with MD2 were established via two key hydrogen bonds and hydrophobic interactions. Furthermore, 10s showed remarkable protective effects against LPS-caused ALI (acute lung injury) in vivo. Taken together, this work provides new lead structures and candidates as MD2 inhibitors for the development of anti-inflammatory drugs.
- Chen, Lingfeng,Jin, Yiyi,Chen, Hongjin,Sun, Chuchu,Fu, Weitao,Zheng, Lulu,Lu, Min,Chen, Pengqin,Chen, Gaozhi,Zhang, Yali,Liu, Zhiguo,Wang, Yi,Song, Zengqiang,Liang, Guang
-
p. 361 - 375
(2017/12/07)
-
- Design, synthesis and neuroprotective activities of novel cinnamide derivatives containing benzylpiperazine moiety
-
A new series of cinnamide derivatives 6a–l were synthesized by the reaction of acyl chlorides with various substituted benzylpiperazines. The structures were characterized by 1H NMR, 13C NMR, and HRMS. The potential neuroprotective activities of cinnamide analogs were evaluated in differentiated rat pheochromocytoma cells (PC12 cells) and in mice subjected to acute cerebral ischemia. Among the series, 6a, 6b, and 6c, featuring a 1,3-benzodioxole moiety, showed potent neuroprotection both in vivo and in vitro. The three compounds were selected and further studied to determine their mechanism of action. MTT assay, Hoechst 33342/PI double staining, and high content screening (HCS) revealed that pretreatment of the cells with 6a, 6b, and 6c has significantly decreased the extent of cell apoptosis in a dose-dependent manner. The results of western blot analysis demonstrated these compounds suppressed apoptosis of glutamate-induced PC12 cells via caspase-3 pathway. These compounds can be lead compounds for further discovery of neuroprotective agents for treating cerebral ischemic stroke.
- Zhong, Yan,Li, Xiaofeng,Zhang, Aixia,Xu, Yi,Li, Ping,Wu, Bin
-
p. 1366 - 1373
(2018/02/28)
-
- Design, synthesis, and anti-inflammatory activity of caffeoyl salicylate analogs as NO production inhibitors
-
Chlorogenic acid (CGA) has been reported to exhibit potent anti-inflammatory activity. However, the development of anti-inflammatory agent based on CGA has not been investigated. In this paper, a series of caffeoyl salicylate compounds derived from CGA were designed, synthesized, and evaluated by LPS-induced nitric oxide synthase inhibition and QRT-PCR technique. Most compounds showed modest activity to inhibit production of nitric oxide (NO) in RAW 264.7 cells induced by lipopolysaccharides (LPS). Among these compounds, QRT-PCR and western blotting results indicated that compounds 6b, 6c, 6f, 6g and D104 that possess 5-member ring or 6-member ring caused a significant inhibition against expression of the iNOS2 in LPS-induced macrophages. In addition, cytotoxic assay displayed most derivatives have good safety in vitro. This new promising scaffold could be further exploited for the development of anti-inflammatory agent in the future.
- Yu, Pan,Xia, Chao-Jie,Li, Dong-Dong,Ni, Jun-Jun,Zhao, Lin-Guo,Ding, Gang,Wang, Zhen-Zhong,Xiao, Wei
-
-
- Optimization of substituted cinnamic acyl sulfonamide derivatives as tubulin polymerization inhibitors with anticancer activity
-
A new series of novel cinnamic acyl sulfonamide derivatives were designed and synthesized and evaluated their anti-tubulin polymerization activities and anticancer activities. One of these compounds, compound 5a with a benzdioxan group, was observed to be an excellent tubulin inhibitor (IC50 = 0.88 μM) and display the best antiproliferative activity against MCF-7 with an IC50 value of 0.17 μg/mL. Docking simulation was performed to insert compound 5a into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent anti-tubulin polymerization activity.
- Luo, Yin,Zhou, Yang,Song, Yanhua,Chen, Guo,Wang, Yu-Xiang,Tian, Ye,Fan, Wei-Wei,Yang, Yu-Shun,Cheng, Tao,Zhu, Hai-Liang
-
supporting information
p. 3634 - 3638
(2018/11/03)
-
- 2,2-dimethylbenzopyran derivative and preparation method and use thereof
-
The invention belongs to the technical field of medicines, and discloses a 2,2-dimethylbenzopyran derivative and a preparation method and use of the 2,2-dimethylbenzopyran derivative. The derivative and pharmaceutically acceptable salt of the derivative have the structural formulae shown in the description, wherein Ar, Ar, X, Y and R1 are as described in the claims and the description. The preparation methods of the derivative and the pharmaceutically acceptable salt of the derivative comprise the following steps: the formula (I) is obtained by mainly taking acetaminophen as a raw material, and subjected to the reactions of Williamson ether formation, cyclization, hydrolysis, amide formation and the like; the formula II is obtained by mainly taking p-hydroxybenzaldehyde as a raw material, and subjected to the reactions of the Williamson ether formation, cyclization, Knoevenagel condensation, amide formation and the like. The derivative and the pharmaceutically acceptable salt ofthe derivative disclosed by the invention can be used for preparing neuroprotective agents and have better neuroprotective effects on ischemic stroke.
- -
-
Page/Page column 13; 14
(2019/01/16)
-
- Total Synthesis and Evaluation of B-Homo Palmatine and Berberine Derivatives as p300 Histone Acetyltransferase Inhibitors
-
Palmatine and berberine, structurally similar isoquinoline alkaloids exhibiting a broad range of biological activities, were recently found to inhibit p300 histone acetyltransferase (HAT), a potential therapeutic target for treating transcriptional activator-driven malignancies and diseases. Here, we report the first total synthesis of B-homo palmatine (11a) and berberine (11b) derivatives, which were synthesized from 3,4-dimethoxybenzaldehyde (1a) and benzo[d][1,3]dioxole-5-carbaldehyde (1b) in nine steps in 13.8 and 16.9 % overall yields, respectively. A number of other new B-homo palmatine and berberine derivatives were also prepared. These derivatives display good inhibitory activity against p300 HAT; compound 12a manifests the most potent inhibition with an IC50 value of 0.42 μm. Cell-based assays revealed that 12a exhibits certain inhibitory activity against HCG27, HT1080, and Z-138 cell lines, and no visible activity towards other cancer cell lines tested, reflecting that 12a has low cytotoxicity and acts against some types of cancer cells.
- Yang, Zhongzhen,Zhang, Yong,Chen, Xin,Li, Weijian,Li, Guo-Bo,Wu, Yong
-
p. 1041 - 1052
(2018/03/06)
-
- High B ring berberine and palmatine derivative synthesis and as the use of reducing blood sugar (by machine translation)
-
The present invention provides a new class of high B ring berberine and palmatine derivative, as shown in the structural formula is shown as: The invention also provides a high B ring berberine and palmatine derivative of preparation and use. The potency test Certificate, the compounds of the invention having good in-vitro hypoglycemic effect, part of the superior to the berberine hydrochloride positive control. The invention high B ring berberine and palmatine derivative potency is prominent, there may be clinical provides a new choice of drug use for. (by machine translation)
- -
-
Paragraph 0007; 0014; 0015
(2018/06/26)
-
- Design, synthesis of N-phenethyl cinnamide derivatives and their biological activities for the treatment of Alzheimer's disease: Antioxidant, beta-amyloid disaggregating and rescue effects on memory loss
-
Gx-50 is a bioactive compound for the treatment of Alzheimer's disease (AD) found in Sichuan pepper (Zanthoxylum bungeanum). In order to find a stronger anti-AD lead compound, 20 gx-50 (1-20) analogs have been designed and synthesized, and their molecular structures were determined based on nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis, as well as comparison with literature data. Compounds 1-20 were evaluated for their anti-AD potential by using DPPH radical scavenging assay for considering their anti-oxidant activity, thioflavin T (ThT) fluorescence assay for considering the inhibitory or disaggregate potency of Ab, and transgenic Drosophila model assay for evaluating their rescue effect on memory loss. Finally, compound 13 was determined as a promising anti-AD candidate.
- Chai, Tian,Zhao, Xiao-Bo,Wang, Wei-Feng,Qiang, Yin,Zhang, Xiao-Yun,Yang, Jun-Li
-
-
- Sinapic acid phenethyl ester as a potent selective 5-lipoxygenase inhibitor: Synthesis and structure–activity relationship
-
Given the hepatotoxicity and an unfavorable pharmacokinetic profile of zileuton (Zyflo), currently the only approved and clinically used 5-Lipoxygenase (5-LO) inhibitor, the search for potent and safe 5-LO inhibitors is highly demanded. The action of several phenolic acid phenethyl esters as potential 5-Lipoxygenase (5-LO) inhibitors has been investigated. For this purpose, a series of 14 phenethyl esters was synthesized and their impact on 5-LO inhibition was evaluated. The effects of position and number of hydroxyl and methoxy groups on the phenolic acid were investigated. The shortening of the linker between the carbonyl and the catechol moiety as well as the presence of the α,β-unsaturated carbonyl group was also explored. The sinapic acid phenethyl ester (10), which can be named SAPE (10) by analogy to caffeic acid phenethyl ester (CAPE), inhibited 5-LO in a concentration-dependent manner and outperformed both zileuton (1) and CAPE (2). With an IC50 of 0.3?μm, SAPE (10) was threefold more potent than CAPE (2) and 10-fold more potent than zileuton (1), the only 5-LO inhibitor approved for clinical use. Unlike CAPE (2), SAPE (10) had no effect on 12-lipoxygenase (12-LO) and less effect on cyclooxygenase 1 (COX-1) which makes it a more selective 5-LO inhibitor.
- Touaibia, Mohamed,Hébert, Martin J. G.,Levesque, Natalie A.,Doiron, Jérémie A.,Doucet, Marco S.,Jean-Fran?ois, Jacques,Cormier, Marc,Boudreau, Luc H.,Surette, Marc E.
-
p. 1876 - 1887
(2018/08/06)
-
- Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides
-
Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of carboxylic acids to aldehydes using the cofactors adenosine triphosphate and nicotinamide adenine dinucleotide phosphate, and have become attractive biocatalysts for organic synthesis. Mechanistic understanding of CARs was used to expand reaction scope, generating biocatalysts for amide bond formation from carboxylic acid and amine. CARs demonstrated amidation activity for various acids and amines. Optimization of reaction conditions, with respect to pH and temperature, allowed for the synthesis of the anticonvulsant ilepcimide with up to 96 % conversion. Mechanistic studies using site-directed mutagenesis suggest that, following initial enzymatic adenylation of substrates, amidation of the carboxylic acid proceeds by direct reaction of the acyl adenylate with amine nucleophiles.
- Wood, Alexander J. L.,Weise, Nicholas J.,Frampton, Joseph D.,Dunstan, Mark S.,Hollas, Michael A.,Derrington, Sasha R.,Lloyd, Richard C.,Quaglia, Daniela,Parmeggiani, Fabio,Leys, David,Turner, Nicholas J.,Flitsch, Sabine L.
-
supporting information
p. 14498 - 14501
(2017/10/18)
-
- Synthesis of some monosaccharide-related ester derivatives as insecticidal and acaricidal agents
-
To develop natural-product-based pesticidal agents, a series of monosaccharide-related ester derivatives (17a–q and 18a–f), glucose (xylose)-piperic acid/piperic acid-like conjugates, were synthesized. Three-dimensional structures of compounds 17b, 17g, 17h, and 17n were unambiguously determined by single-crystal X-ray diffraction. Especially compounds 18e and 18f exhibited the most potent insecticidal and acaricidal activities against Mythimna separata and Tetranychus cinnabarinus. Their structure-activity relationships were also discussed.
- Huang, Xiaobo,Zhang, Bingchuan,Xu, Hui
-
p. 4336 - 4340
(2017/09/12)
-
- Synthesis and biological evaluation of phenylpropanoid derivatives
-
In this work, a series of oxime ether phenylpropanoid derivatives were synthesized. Their anti-hepatitis B virus (HBV) activity in HepG 2.2.15 cells was determined, and anti-cancer potential against three human cancer cell lines was evaluated. All the synthesized derivatives showed great efficiency against HBV. Compound 4d demonstrated the most effective anti-HBV activity, performing strong potent inhibitory not only on the secretion of HBsAg (IC50?=?50.45?μM, SI?=?9.18) and HBeAg (IC50?=?50.11?μM, SI?=?9.24), but also on the HBV DNA replication (IC50?=?51.80?μM, SI?=?8.94). Besides, the synthetic compounds also displayed obvious anti-cancer activity. Moreover, the docking study of all synthesized compounds inside the related protein active site was conducted to explore the molecular interactions and a molecular target for activity using a MOE-docking technique. This study identified a new class of potent anti-HBV and anti-cancer agents.
- Liu, Sheng,Li, Yubin,Wei, Wanxing,Wei, Jingchen
-
p. 1074 - 1086
(2016/07/06)
-
- Synthesis and biological evaluation of (E)-cinnamic acid, (E)-2-styrylthiazole and (E)-2-[2-(naphthalen-1-yl)vinyl]thiazole derivatives
-
Cinnamyl- and thiazole-based compounds have been shown to exhibit diverse medicinal properties and a series of twelve (E)-2-styrylthiazole and (E)-2-[(naphthalen-1-yl)vinyl]thiazole derivatives, which are conjugates of both systems and which satisfy the "Lipinski rule of 5", have been synthesised and subjected to in vitro biological screening. While insignificant inhibition (60-98% viability at 10 μM) of HeLa (cervical cancer) cells was noted, all five of the (E)-2-[naphthalen-1- yl)vinyl]thiazole derivatives proved remarkably active against SH-SY5Y (neuroblastoma) cells with IC50 values ranging from 2.09 to 8.64 μM. Two of the seven (E)-2-styrylthiazoles were found to be moderately active (with IC50 values of 10.8 and 11.7 mM), whereas the remaining five analogues exhibit significant proliferation of SH-SY5Y cells (with IC50 values of 180-1000 mM). The results warrant further studies on the effects of styrylthiazoles on the differentiation and extension of SH-SY5Y cells in order to assess their activity in neurological degenerative diseases.
- Olawode, Emmanuel O.,Tandlich, Roman,Prinsloo, Earl,Isaacs, Michelle,Hoppe, Heinrich,Seldon, Ronnett,Warner, Digby F.,Steenkamp, Vanessa,Kaye, Perry T.
-
p. 284 - 296
(2018/03/09)
-
- Synthesis and biological evaluation of (E)-cinnamic acid, (E)-2-styrylthiazole and (E)-2-[2-(naphthalen-1-yl)vinyl]thiazole derivatives
-
Cinnamyl- and thiazole-based compounds have been shown to exhibit diverse medicinal properties and a series of twelve (E)-2-styrylthiazole and (E)-2-[(naphthalen-1-yl)vinyl]thiazole derivatives, which are conjugates of both systems and which satisfy the “Lipinski rule of 5”, have been synthesised and subjected to in vitro biological screening. While insignificant inhibition (60-98% viability at 10 μM) of HeLa (cervical cancer) cells was noted, all five of the (E)-2-[naphthalen-1-yl)vinyl]thiazole derivatives proved remarkably active against SH-SY5Y (neuroblastoma) cells with IC50 values ranging from 2.09 to 8.64 μM. Two of the seven (E)-2-styrylthiazoles were found to be moderately active (with IC50 values of 10.8 and 11.7 mM), whereas the remaining five analogues exhibit significant proliferation of SH-SY5Y cells (with IC50 values of 180-1000 mM). The results warrant further studies on the effects of styrylthiazoles on the differentiation and extension of SH-SY5Y cells in order to assess their activity in neurological degenerative diseases.
- Olawode, Emmanuel O.,Tandlich, Roman,Prinsloo, Earl,Isaacs, Michelle,Hoppe, Heinrich,Seldon, Ronnett,Warner, Digby F.,Steenkamp, Vanessa,Kaye, Perry T.
-
p. 284 - 296
(2018/05/09)
-
- Design, synthesis, molecular docking studies and anti-HBV activity of phenylpropanoid derivatives
-
In this work, a series of phenylpropanoid derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated. Most of the synthesized derivatives showed effective anti-HBV activity. And compound 4d-3 showed the most effective anti-HBV activity, performing strong potent inhibitory not only on the secretion of HBsAg (IC50 = 58.28 μM, SI = 23.26) and HBeAg (IC50 = 97.21 μM, SI = 13.95), but also on the HBV DNA replication (IC50 = 42.28 μM, SI = 32.06). The structure-activity relationships (SARs) of the derivatives had been discussed, which were useful for developing phenylpropanoid derivatives as novel anti-HBV agents. Moreover, the docking study of all synthesized compounds inside the HLA-A protein (PDB ID: 3OX8) active site was carried out to explore the molecular interactions and a molecular target for activity and a modified assay method measuring the interaction between our derivatives and HBcAg was investigated, indicating that the HBV core protein might be their potential target for anti-HBV. This study identified a new class of potent non-nucleoside anti-HBV agents.
- Liu, Sheng,Li, Yubin,Wei, Wanxing,Wang, Kuiwu,Wang, Lisheng,Wang, Jianyi
-
-
- Sodium valproate drug intermediate 3,4-methylenedioxy cinnamic acid synthesis method
-
The invention relates to a sodium valproate drug intermediate 3,4-methylenedioxy cinnamic acid synthesis method, which comprises: in a reaction container provided with a stirrer and a reflux condenser, adding 1.5 mol of a 3,4-methylenedioxyphenyl bromide methanol solution, 0.56 mol of cuprous chloride, 1.7-1.9 mol of a malonic acid solution, 310 ml of acetonitrile, and 230 ml of nitromethane, controlling the stirring speed at 130-160 rpm, heating the solution to achieve a temperature of 60-65 DEG C, carrying out reflux for 3-6 h, reducing the solution temperature to 40-45 DEG C, continuously carrying out the reaction for 90-110 min, reducing the solution temperature to 11-17 DEG C, adding 800 ml of an oxalic acid solution, standing for 6-8 h, precipitating the solid, filtering, washing with a salt solution, washing with toluene, washing with ethylenediamine, dewatering with a dewatering agent, and re-crystallizing in p-xylene to obtain the crystal 3,4-methylenedioxy cinnamic acid.
- -
-
Paragraph 0007; 0008; 0016; 0017
(2016/10/24)
-
- Design, synthesis, biological evaluation and molecular docking studies of phenylpropanoid derivatives as potent anti-hepatitis B virus agents
-
A series of phenylpropanoid derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the synthesized derivatives showed effective anti-HBV activity. Of these compounds, compound 4c-1 showed the most potent anti-HBV activity, demonstrating potent inhibitory effect not only on the secretion of HBsAg (IC50 = 14.18 μM, SI = 17.85) and HBeAg (IC50 = 6.20 μM, SI = 40.82) secretion but also HBV DNA replication (IC50 = 23.43 μM, SI = 10.80). The structureeactivity relationships (SARs) of phenylpropanoid derivatives had been discussed, which were useful for phenylpropanoid derivatives to be explored and developed as novel anti-HBV agents. Moreover, the docking study of all synthesized compounds inside the HLA-A protein (PDB ID: 3OX8) active site were carried out to explore the molecular interactions and a molecular target for activity of phenylpropanoid derivatives with the protein using a moe-docking technique. This study identified a new class of potent anti-HBV agents.
- Liu, Sheng,Wei, Wanxing,Li, Yubin,Liu, Xu,Cao, Xiaoji,Lei, Kechan,Zhou, Min
-
p. 473 - 482
(2015/04/14)
-
- Chiral Cyclopentadienyl Iridium(III) Complexes Promote Enantioselective Cycloisomerizations Giving Fused Cyclopropanes
-
The cyclopentadienyl (Cp) group is a very important ligand for many transition-metal complexes which have been applied in catalysis. The availability of chiral cyclopentadienyl ligands (Cpx) lags behind other ligand classes, thus hampering the investigation of enantioselective processes. We report a library of chiral CpxIrIII complexes equipped with an atropchiral Cp scaffold. A robust complexation procedure reliably provides CpxIrIII complexes with tunable counterions. In a proof-of-concept application, the iodide-bearing members are shown to be highly selective for enyne cycloisomerization reactions. The dehydropiperidine-fused cyclopropane products are formed in good yields and enantioselectivities.
- Dieckmann, Michael,Jang, Yun-Suk,Cramer, Nicolai
-
supporting information
p. 12149 - 12152
(2015/10/12)
-
- Application of chiral ligands: Carbohydrates, nucleoside-lanthanides and other Lewis acid complexes to control regio- and stereoselectivity of the dipolar cycloaddition reactions of nitrile oxides and esters
-
Chiral Lewis acid mediated 1,3-dipolar cycloaddition reactions of 4-trifluoromethylbenzonitrile oxide to methyl crotonate as well to β-substituted acrylates and (Z)-pent-2-en-1-yl esters were examined. Excellent enantioselectivities with moderate to good regioselectivities were achieved for crotonates with complexes of BiBr3 with (+)-(4,6-benzylidene)methyl-α-d-glucopyranoside C, with the l-ascorbic acid I-FeCl3 system, and with lipase Candida antarctica. High enantiomeric excess was observed for isopropyl ester and benzyl ester. The outstanding ee values were achieved for acrylates with β-t-butyl, cyclohexyl, and 1,3-benzodioxol-5-yl groups in cycloadditions catalyzed by C-Yb(OTf)3 and the (+)-2-hydroxy-3-pinanone N-TiCl4 system. High enantioselectivities were found in reactions of (Z)-pent-2-en-1-yl esters mediated by complexes N-Mg(OTf)2 and N-TiCl4.
- Gucma, Miroslaw,Golbiewski, W. Marek,Krawczyk, Maria
-
p. 13112 - 13124
(2015/02/19)
-
- TiCl4-mediated olefination of aldehydes with acetic acid and alkyl acetates: A stereoselective approach to (E)-α,β-unsaturated carboxylic acids and esters
-
A new method has been developed for the preparation of α,β- unsaturated carboxylic acids and corresponding esters with (E)-stereoselectivity via the TiCl4-mediated olefination of aldehydes. The method, which uses readily available acetic acid or its alkyl esters as active methylene partners, is more flexible and complementary to conventional routes in the preparation of (E)-cinnamic acid derivatives.
- Augustine, John Kallikat,Boodappa, Chandrakantha,Venkatachaliah, Srinivasa,Mariappan, Ayyampillai
-
p. 3503 - 3506
(2014/06/10)
-
- Regioselective route for arylnaphthalene lactones: Convenient synthesis of taiwanin C, justicidin E, and daurinol
-
Arylnaphthalene lactones are natural products which can be isolated from a wide range of plants and have the significant biological activities including cytotoxicity, antimicrobial, diuretic, and ion channel blocking. The drawback of the previous intramolecular Diels-Alder reaction of 3-arylprop-2-ynyl 3-arylpropiolates was to generate two regioisomers of arylnaphthalene lactone without selectivity. Herein, we report a convenient and regioselective synthesis method in which the intramolecular Diels-Alder reaction of an arylalkene-arylalkyne and subsequent DDQ oxidation was used for Type I and Type II arylnaphthalene lactones, respectively. We demonstrated the synthesis of three lignans, taiwanin C (Type I), justicidin E (Type II), and daurinol (Type I and anti-cancer activity).
- Park, Ju-Eun,Lee, Juyeun,Seo, Seung-Yong,Shin, Dongyun
-
p. 818 - 820
(2014/02/14)
-
- SUBSTITUTED CINNAMAMIDE DERIVATIVE, PREPARATION METHOD AND USE THEREOF
-
The present invention relates to substituted cinnamamide derivatives, the method for preparing thereof and the use thereof. Each of said derivatives has a structure of formula (I). The method for preparing the substituted cinnamamides and their derivatives of the present invention is also disclosed. Substituted piperonal derivatives are selected as starting materials to prepare the substituted cinnamamide derivatives of the present invention by Wittig reaction and acid-amine condensation reaction. Further, a use of the present compounds in preventing and treating depressive-type mental diseases is disclosed.
- -
-
Paragraph 0142; 0143
(2014/05/08)
-
- Alum-Cs2CO3 as a new recyclable solid base catalyst for the efficient syntheses of arylidenemalononitriles, esters and arylcinnamic acids in water
-
The condensation between aromatic aldehydes and malononitrile, ethylcyanoacetate and malonic acid for the syntheses of arylidenemalononitriles, arylidenemalonic acid esters and aryl cinnamic acids in water using alum-Cs2CO3 as a solid support catalyst has been described. Alum-Cs2CO3 was found to be a highly active, stable and recyclable catalyst under reaction conditions.
- Taduri, Ashok Kumar,Devi, B. Rama
-
p. 1938 - 1942
(2014/06/09)
-
- A versatile total synthesis of 8-oxyberberine and oxohomoberberines
-
The total syntheses of 8-oxyberberine and oxohomoberberines were accomplished starting from commercially available 5-bromobenzo[d][1,3]dioxole, piperonal and sesamol in high total yield. The key steps involved a modified Pomeranz-Fritsch reaction and the intramolecular Heck cyclization. This approach is short, convenient and suitable for the preparation of homoberberine analogues.
- He, Yun,Zheng, Yang,Hai, Li,Wu, Yong
-
p. 1121 - 1127
(2015/01/16)
-
- Asymmetric synthesis of 1-aza-4-deoxypicropodophyllotoxin
-
In our search for new easily accessible analogues based on the natural product podophyllotoxin, we synthesized 1-aza-4-deoxypicropodophyllotoxin in good overall yield and excellent enantioselectivity. The synthesis was centered around a direct asymmetric Mannich reaction using d-proline as the key step for introduction of the chiral centres. Our synthesis of 1-aza-4- deoxypodophyllotoxin was hindered through the increased instability towards epimerization of the C2 position. We did, however, synthesized a new scaffold based on the opened lactone analogue. Georg Thieme Verlag Stuttgart New York.
- Aigret, Benoit M.,Jacobs, Jeroen,Van Meervelt, Luc,De Borggraeve, Wim M.
-
supporting information
p. 1097 - 1100
(2013/06/27)
-
- Solvent-dependent regioselective oxidation of trans-chalcones using aqueous hydrogen peroxide
-
A novel method for regioselective oxidation of trans-chalcones with hydrogen peroxide in acetonitrile to afford cinnamic acids is reported. Only trans-β-arylacrylic acids were observed. A wide range of functionalized products can be effectively produced from various chalcones in good to excellent yields.
- Wang, Peng,Cai, Jin,Yang, Jiabin,Sun, Chunlong,Li, Lushen,Ji, Min
-
p. 518 - 522
(2013/08/25)
-
- β-alanine-DBU: A highly efficient catalytic system for knoevenagel-doebner reaction under mild conditions
-
A mild and efficient Knoevenagel-Doebner reaction from malonic acid and a wide range of aldehydes was catalyzed by a catalytic system consisting of β-alanine and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), affording the corresponding (E)-α,β-unsaturated carboxylic acids in good to excellent yields and with high stereoselectivity. The advantage of the method is that the reaction could proceed smoothly at ambient temperature so that it can tolerate a variety of functional groups and avoid unnecessary side reactions. Copyright
- Zhu, Lingjian,Lei, Ning,Miao, Zhenyuan,Sheng, Chunquan,Zhuang, Chunlin,Yao, Jianzhong,Zhang, Wannian
-
experimental part
p. 139 - 143
(2012/03/09)
-
- First total synthesis of Papilistatin
-
Papilistatin has been isolated recently and found to have good anticancer and antibacterial activity. Papilistatin is a unique phenanthrene-1,10- dicarboxylic acid. The first total synthesis of papilistatin is described here with radical cyclisation as the key step.
- Wu, Meng,Li, Ling,Feng, An-Zheng,Su, Bo,Liang, De-Min,Liu, Yu-Xiu,Wang, Qing-Min
-
scheme or table
p. 2539 - 2542
(2011/05/06)
-
- Amides from Piper capense with CNS activity - A preliminary SAR analysis
-
Piper capense L.f. (Piperaceae) is used traditionally in South Africa as a sleep inducing remedy. Bioassay-guided fractionation of the roots of P. capense led to the isolation of piperine (1) and 4,5-dihydropiperine (2), which showed moderate affinity for the benzodiazepine site on the GABAA receptor (IC50 values of 1.2 mM and 1.0 mM, respectively). The present study suggests that strict structural properties of the amides are essential for affinity. Taken together, these observations suggest that the carbon chain must contain not less than four carbons, and that a conjugated double bond, adjacent to the amide group, is necessary for binding to the receptor and that the amine part should be bulky.
- Pedersen, Mikael E.,Metzler, Bjorn,Stafford, Gary I.,Van Staden, Johannes,Jaeger, Anna K.,Rasmussen, Hasse B.
-
experimental part
p. 3833 - 3843
(2009/12/26)
-
- Design and synthesis of novel 2-phenylaminopyrimidine (PAP) derivatives and their antiproliferative effects in human chronic myeloid leukemia cells
-
A series of novel 2-phenylaminopyrimidine (PAP) derivatives structurally related to STI-571 were designed and synthesized. The abilities of these compounds to inhibit proliferation were tested in human chronic myeloid leukemia K562 cells. (E)-3-(2-bromophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2- ylamino)phenyl]acrylamide( 12d) was the most effective cell growth inhibitor and was 3-fold more potent than STI-571.
- Chang, Sheng,Yin, Shi-Liang,Wang, Jian,Jing, Yong-Kui,Dong, Jin-Hua
-
experimental part
p. 4166 - 4179
(2009/12/28)
-
- ANTI CANCER USE OF CAFFEIC ACID AND DERIVATIVES
-
The present invention relates to the use of caffeic acid or a derivative thereof represented by the following general formula (1 ) wherein X is O, NH, or heterocyclyl; R may be present or absent and if present, is H, alkyl, aryl, or heterocyclyl; in all its stereoisomeric and tautomeric forms, and mixtures thereof in all ratios, and a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, pharmaceutically acceptable polymorph or a prodrug, in the treatment of chronic myeloid leukemia (CML) which is resistant to treatment with Gleevec. The invention also relates to a method for reducing the proliferation of cells that are resistant to Gleevec by contacting the cells with a compound of general formula (1 ). The present invention also relates to pharmaceutical compositions (for the manufacture of the medicament) including caffeic acid or a derivative or a salt thereof represented by the general formula (1 ) for the treatment of chronic myeloid leukemia (CML) that is resistant to treatment with Gleevec, or for reducing the proliferation of cells that are resistant to Gleevec. The present invention further relates to a method of treatment of chronic myeloid leukemia (CML) that is resistant to treatment with Gleevec.
- -
-
Page/Page column 16-17
(2008/06/13)
-
- Novel 1,3,4-thiadiazolium-2-phenylamine chlorides derived from natural piperine as trypanocidal agents: Chemical and biological studies
-
We herein describe the synthesis and characterization of nine new 1,3,4-thiadiazolium-2-phenylamine chlorides derived from natural piperine. We evaluate their toxic effects against the different evolutive forms of Trypanosoma cruzi, and the host cell (murine macrophages). The results obtained show that mesoionic hydrochloride MI possesses the best activity profile. Compound MI may be a prototype for use in the development of a new chemotherapeutic agent with high efficiency, which may be employed in the treatment of Chagas' disease.
- da Silva Ferreira, Welisson,Freire-de-Lima, Leonardo,Saraiva, Victor Barbosa,Alisson-Silva, Frederico,Mendonca-Previato, Lucia,Previato, Jose Osvaldo,Echevarria, Aurea,de Lima, Marco Edilson Freire
-
p. 2984 - 2991
(2008/09/19)
-
