- Synthesis and antibacterial activity of novel Schiff bases of thiosemicarbazone derivatives with adamantane moiety
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Increased bacterial resistance to antibiotics is a major threat to human health, and it is particularly important to develop novel antibiotic drugs. Here, we designed a series of Schiff base thiosemicarbazone derivatives containing an adamantane moiety, and carried out the structural characterization of the compounds and in vitro antibacterial activity tests. Compound 7e was as effective as the commonly used antibiotic ampicillin against the Gram-negative bacterium Escherichia coli, and compound 7g had a good inhibitory effect against Gram-positive Bacillus subtilis. These findings provide data for the development of better thiosemicarbazone antibacterial agents.
- Zhu, Jiahui,Teng, Guosheng,Li, Dongfeng,Hou, Ruibin,Xia, Yan
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p. 1534 - 1540
(2021/06/16)
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- Discovery of a Pyrimidinedione Derivative as a Potent and Orally Bioavailable Axl Inhibitor
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The receptor tyrosine kinase Axl plays important roles in promoting cancer progression, metastasis, and drug resistance and has been identified as a promising target for anticancer therapeutics. We used molecular modeling-assisted structural optimization starting with the low micromolar potency compound 9 to discover compound 13c, a highly potent and orally bioavailable Axl inhibitor. Selectivity profiling showed that 13c could inhibit the well-known oncogenic kinase Met with equal potency to its inhibition of Axl superfamily kinases. Compound 13c significantly inhibited cellular Axl and Met signaling, suppressed Axl- and Met-driven cell proliferation, and restrained Gas6/Axl-mediated cancer cell migration or invasion. Furthermore, 13c exhibited significant antitumor efficacy in Axl-driven and Met-driven tumor xenograft models, causing tumor stasis or regression at well-tolerated doses. All these favorable data make 13c a promising therapeutic candidate for cancer treatment.
- Zhang, Hefeng,Peng, Xia,Dai, Yang,Shao, Jingwei,Ji, Yinchun,Sun, Yiming,Liu, Bo,Cheng, Xu,Ai, Jing,Duan, Wenhu
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supporting information
p. 3956 - 3975
(2021/04/12)
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- Synthesis and Antiproliferative Activity of New Thiosemicarboxamide Derivatives
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To discover new anticancer agents, two series of thiosemicarboxamide derivatives were synthesized and evaluated for their antiproliferative activity against human cancer cells in vitro. Most target compounds (especially 3f, 3g, and 3h) exhibit potent antiproliferative activity against HeLa cells. Importantly, compound 3h, bearing a 4-methylphenyl substituent at N position of thiourea moiety, has significant and broad-spectrum inhibitory activities against cancer cells (HepG2, HeLa, MDA-MB231, A875, and H460 cells) with low IC50 values (5.0 μM) and shows low toxicity to normal LO2 and MRC-5 cells. Further studies show that compound 3h exerts high inhibitory activity in cancer cells by inducing the G2/M-phase arrest of cancer cells. Collectively, this study presents compound 3h as a new entity for the development of cell cycle arrest inducers for the treatment of cancer.
- Chen, Jun,Fang, Meijuan,Guo, Yafei,Hu, Hongyu,Hu, Sangsang,Sun, Ke,Wu, Jun,Xue, Yuhua
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- Preparation and application of thiosemicarbazone compound
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The invention discloses a thiosemicarbazone compound, and biological activity analysis is carried out on the thiosemicarbazone compound. The invention also discloses application of the thiosemicarbazone compound in preparation of antibacterial drugs. According to the invention, important intermediates 6a-6h are synthesized from hydrazine hydrate and react with adamantane benzaldehyde respectivelyto synthesize eight adamantane aromatic aldehyde thiosemicarbazone compounds, the structures of the compounds can be confirmed by infrared, nuclear magnetic hydrogen spectrum, carbon spectrum and massspectrum methods, and the antibacterial activity of the compounds is tested in vitro. The result shows that the compound has a good antibacterial effect on escherichia coli and bacillus subtilis.
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Paragraph 0010; 0014; 0015
(2021/02/20)
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- Synthesis, cytotoxicity, and in vivo antitumor activity study of parthenolide semicarbazones and thiosemicarbazones
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Parthenolide is an important sesquiterpene lactone with potent anticancer activities. In order to further improve its biological activity, a series of parthenolide semicarbazone or thiosemicarbazone derivatives was synthesized and evaluated for their anti
- Du, Guohua,Jia, Xinxin,Li, Yan,Liu, Qi,Wang, Shiyi,Zeng, Binglin,Zhang, Chen
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- Synthesis, characterization, and antioxidant activity of some new N 4-arylsubstituted-5-methoxyisatin-β-thiosemicarbazone derivatives
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Abstract: Firstly, thiosemicarbazides were prepared by the reaction of hydrazine monohydrate with isothiocyanates in cold dry ethanol at 0?°C for 1?h. After that, new isatin-β-thiosemicarbazones were synthesized by treatment of 5-methoxyisatin with thiose
- Mu?lu, Halit
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p. 2083 - 2098
(2020/01/13)
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- Synthesis, molecular modeling and antiviral activity of novel 5-fluoro-1H-indole-2,3-dione 3-thiosemicarbazones
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In this work, novel 5-fluoro-1-methyl/ethyl-1H-indole-2,3-dione 3-[4-(substituted phenyl)-thiosemicarbazones] 6a-n and 7a-n were synthesized. The antiviral effects of the compounds were tested against HSV-1 (KOS), HSV-2 (G) HSV-1 TK- KOS ACVr and VV in HEL cell cultures using acyclovir and ganciclovir as standards, and Coxsackie B4 virus in Vero cell cultures using ribavirin and mycophenolic acid as standards. R2 ethyl substituted 7 derivatives were found effective against viruses tested. R1 4-CF3 substituted 7d, R1 4-OCH3 substituted 7 g and R1 3-Cl substituted 7 l showed activity against HSV-1 (KOS), HSV-2 (G) HSV-1 TK- KOS ACVr and VV. Whereas only R1 4-Br substituted 7n has selective activity against coxsackie B4 virus. Molecular modeling studies of 7d and 7l were performed to determine binding side on HSV-1 glycoprotein B and D, HSV-2 glycoprotein B structures.
- ?zbil, Mehmet,Duran, Gizem Nur,Karal?, Nilgün,Sevin?li, Zekiye ?eyma
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- Preparation, structure elucidation, and antioxidant activity of new bis(thiosemicarbazone) derivatives
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Schiff-base–bearing new bis(thiosemicarbazone) derivatives were prepared from terephthalaldehyde and various thiosemicarbazides. FT–IR, 1 H NMR, 13 C NMR, and UV–Vis spectroscopic methods and elemental analysis were used to elucidate
- Yakan, Hasan
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p. 1085 - 1099
(2020/09/16)
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- Functionalized Oxoindolin Hydrazine Carbothioamide Derivatives as Highly Potent Inhibitors of Nucleoside Triphosphate Diphosphohydrolases
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Ectonucleoside triphosphate diphosphohydrolases (NTPDases) are ectoenzymes that play an important role in the hydrolysis of nucleoside triphosphate and diphosphate to nucleoside monophosphate. NTPDase1, -2, -3 and -8 are the membrane bound members of this enzyme family that are responsible for regulating the levels of nucleotides in extracellular environment. However, the pathophysiological functions of these enzymes are not fully understood due to lack of potent and selective NTPDase inhibitors. Herein, a series of oxoindolin hydrazine carbothioamide derivatives is synthesized and screened for NTPDase inhibitory activity. Four compounds were identified as selective inhibitors of h-NTPDase1 having IC50 values in lower micromolar range, these include compounds 8b (IC50 = 0.29 ± 0.02 μM), 8e (IC50 = 0.15 ± 0.009 μM), 8f (IC50 = 0.24 ± 0.01 μM) and 8l (IC50 = 0.30 ± 0.03 μM). Similarly, compound 8k (IC50 = 0.16 ± 0.01 μM) was found to be a selective h-NTPDase2 inhibitor. In case of h-NTPDase3, most potent inhibitors were compounds 8c (IC50 = 0.19 ± 0.02 μM) and 8m (IC50 = 0.38 ± 0.03 μM). Since NTPDase3 has been reported to be associated with the regulation of insulin secretion, we evaluated our synthesized NTPDase3 inhibitors for their ability to stimulate insulin secretion in isolated mice islets. Promising results were obtained showing that compound 8m potently stimulated insulin secretion without affecting the NTPDase3 gene expression. Molecular docking studies of the most potent compounds were also carried out to rationalize binding site interactions. Hence, these compounds are useful tools to study the role of NTPDase3 in insulin secretion.
- Afzal, Saira,Hameed, Abdul,Iqbal, Jamshed,Pelletier, Julie,Sévigny, Jean,al-Rashida, Mariya
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- INDOLE-OXADIAZOLE COMPOUNDS AND THEIR THERAPEUTIC USE
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The present application pertains to methods of using indole-oxadiazole compounds of Formula I to modulate cannabinoid receptor activity: I In particular diseases, disorders or conditions that benefit from modulating cannabinoid receptor activity, such as non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), schizophrenia, bipolar disorder, psychosis, metabolic syndrome, type-2 diabetes, dyslipidaemia, obesity, eating disorders, cardiovascular diseases and disorders, and other conditions as described herein, may be treated. Also included in the present application are certain novel compounds of Formula Ia and pharmaceutical compositions comprising these compounds.
- -
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Paragraph 00184; 00189; 00204
(2020/05/07)
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- Containing trifluoromethyl and piperazine triazole Mannich alkali compound and its preparation and use
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The invention belongs to the field of agricultural bactericides and herbicides, and particularly discloses triazole Mannich base compounds containing trifluoromethyl and piperazine, as well as preparation methods and application of the triazole Mannich ba
- -
-
Paragraph 0035-0039
(2019/03/21)
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- Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition
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Twelve 2-(quinolin-4-ylmethylene) hydrazinecarbothioamide derivatives were synthetized and their biological properties were investigated, among which, the ability to interact with DNA and BSA through UV–Vis absorption, fluorescence, Circular Dichroism, molecular docking and relative viscosity, antiproliferative activity against MCF-7 and T-47D mammary tumor cells and RAW-264.7 macrophages and inhibitory capacity of the enzyme topoisomerase IIα. In the binding study with DNA and BSA, all the compounds displayed affinity for interaction with both biomolecules, especially JF-92 (p-ethyl-substituted), with binding constant of 1.62 × 106 and 1.43 × 105, respectively, and DNA binding mode by intercalation. The IC50 values were obtained between 0.81 and 1.48 μM and topoisomerase inhibition results in 10 μM. Thus, we conclude that the reduction of the acridine to quinoline ring did not disrupt the antitumor action and that substitution patterns are important for biomolecule interaction affinity as they demonstrate the potential of these compounds for anticancer therapy.
- Ribeiro, Amélia Galdino,Almeida, Sinara M?nica Vitalino de,de Oliveira, Jamerson Ferreira,Souza, Tulio Ricardo Couto de Lima,Santos, Keriolaine Lima dos,Albuquerque, Amanda Pinheiro de Barros,Nogueira, Mariane Cajuba de Britto Lira,Carvalho Junior, Luiz Bezerra de,Moura, Ricardo Olímpio de,da Silva, Aline Caroline,Pereira, Valéria Rêgo Alves,Castro, Maria Carolina Accioly Brelaz de,Lima, Maria do Carmo Alves de
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- Synthesis of novel triazinoindole-based thiourea hybrid: A study on α-glucosidase inhibitors and their molecular docking
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A new class of triazinoindole-bearing thiosemicarbazides (1-25) was synthesized and evaluated for α-glucosidase inhibitory potential. All synthesized analogs exhibited excellent inhibitory potential, with IC50 values ranging from 1.30 ± 0.01 to 35.80 ± 0.80 μM when compared to standard acarbose (an IC50 value of 38.60 ± 0.20 μM). Among the series, analogs 1 and 23 were found to be the most potent, with IC50 values of 1.30 ± 0.05 and 1.30 ± 0.01 μM, respectively. The structure- activity relationship (SAR) was mainly based upon bringing about different substituents on the phenyl rings. To confirm the binding interactions, a molecular docking study was performed.
- Taha, Muhammad,Alshamrani, Foziah J.,Rahim, Fazal,Hayat, Shawkat,Ullah, Hayat,Zaman, Khalid,Imran, Syahrul,Khan, Khalid Mohammed,Naz, Farzana
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- 3-[(E)-(acridin-9′-ylmethylidene)amino]-1-substituted thioureas and their biological activity
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This paper describes the synthesis of a novel series of acridine thiosemicarbazones through a two-step reaction between various isothiocyanates and hydrazine followed by treatment with acridin-9-carbaldehyde. The properties of this series of seven new derivatives are studied using NMR and biochemical techniques, and the DNA-binding properties of the compounds are determined using spectrophotometric studies (UV–vis absorption, fluorescence, and circular/linear dichroism) and viscometry. The binding constants K are estimated as being in the range of 2.2 to 7.8?×?104?M??1 and the percentage of hypochromism was found to be 22.11–49.75% (from UV–vis spectral titration). Electrophoretic experiments prove that the novel compounds demonstrate moderate inhibitory effects against Topo I activity at a concentration of 60?×?10??6?M.
- Be?ka, Michal,Vilková, Mária,Salem, Othman,Ka?párková, Jana,Brabec, Viktor,Ko?urková, Mária
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p. 234 - 241
(2017/03/23)
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- Design, synthesis and biological evaluation of novel thiosemicarbazide analogues as potent anticonvulsant agents
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Novel thiosemicarbazide derivatives were synthesised and evaluated for their anticonvulsant activity and neurotoxicity. Anticonvulsant activity was done for grand mal and petit mal types of epilepsies by maximal electroshock (MES) and pentylenetetrazol (P
- Nevagi, Reshma J.,Dhake, Avinash S.,Narkhede, Harsha I.,Kaur, Prabhjeet
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- Thiosemicarbazide, a fragment with promising indolamine-2,3-dioxygenase (IDO) inhibition properties
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With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.
- Serra, Silvia,Moineaux, Laurence,Vancraeynest, Christelle,Masereel, Bernard,Wouters, Johan,Pochet, Lionel,Frédérick, Rapha?l
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- Chemoselective route for synthesis of N-aryl-3-oxochromeno[2,3-c]pyrazole- 2(3H)-carbothioamide derivatives
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A chemoselective route for the synthesis of chromeno[2,3-c]pyrazole-2(3H)- carbothioamide derivatives by a five-component reaction of salicylaldehyde, malononitrile, NH2NH2·H2O, aryl isothiocyanate, and H2O in EtOH/AcOH mixture is reported. This new protocol has the advantages of high yields, short reaction times, ease of operation, and simple purification. All structures were confirmed by IR, 1H- and 13C-NMR, and MS analyses. A plausible mechanism for this type of reaction is proposed (Scheme 2). Copyright
- Alizadeh, Abdolali,Ghanbaripour, Rashid
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p. 895 - 899
(2014/07/07)
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- Synthesis and biological evaluation of 4-phenoxy-6,7-disubstituted quinolines possessing semicarbazone scaffolds as selective c-Met inhibitors
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Novel quinoline derivatives bearing acyclic semicarbazones were prepared and their chemical structures as well as the relative stereochemistry were confirmed. All the synthesized compounds were evaluated for their c-Met kinase inhibitory activity and their cytotoxicity against the cell lines HT-29, MKN-45, and MDA-MB-231 in vitro. Several potent compounds were further evaluated against A549 cells. Most compounds displayed moderate to excellent activity, and the structure-activity relationship studies identified the most promising compound 35 as a selective c-Met kinase inhibitor (IC50 = 4.3 nM). Compound 35 showed a 3.5- and 18.8-fold increase in cytotoxicity in vitro against HT-29 and A549 cells, respectively, compared to that of foretinib. Poor off-target effects of compound 35 were further confirmed by the antiproliferative activity against the c-Met inhibition less sensitive MDA-MB-231 cell line (IC50 = 0.77 μM). Copyright
- Qi, Baohui,Tao, Haiyan,Wu, Di,Bai, Jinying,Shi, Yandan,Gong, Ping
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p. 596 - 609
(2013/09/02)
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- Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothio amides
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Thirty six new N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothioamides were synthesized and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity was established in three seizure models i.e. MES, scMET and 6 Hz model. The most active compound was 2-[4-(4-chlorophenoxy)benzylidene]-N-(4-fluorophenyl) hydrazinecarbothioamide PC 31 which showed 100% protection at 0.5 h in the 6 Hz test. Compound 2-[4-(4-bromophenoxy) benzylidene]-N-(4-bromophenyl) hydrazinecarbothioamide PC 23 was found to be active in both the MES and 6 Hz test. A computational study was carried out from calculation of a pharmacophore pattern and the prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta and GABA (A) alpha-1 receptors, in the Lamarckian genetic algorithm based on flexible docking studies.
- Tripathi, Laxmi,Kumar, Praveen,Singh, Ranjit,Stables, James P.
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experimental part
p. 153 - 166
(2012/03/09)
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- Microwave-assisted synthesis and antibacterial activity of novel chenodeoxycholic acid thiosemicarbazone derivatives
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A rapid and efficient method for the synthesis of novel chenodeoxycholic acid thiosemicarbazone derivatives under solvent-free conditions using microwave irradiation is reported. Ten novel compounds have been synthesised in good yields. Their structures were elucidated by 1H NMR, IR, ESI-MS spectra and elemental analysis. Preliminary results showed that some of these compounds possess inhibitory effects against S. typhimurium and E. coli.
- Qiu, Liying,Shi, Zhichuan,Mei, Qinggang,Zhao, Zhigang
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experimental part
p. 456 - 459
(2011/11/06)
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- Isatin-β-thiosemicarbazones as potent herpes simplex virus inhibitors
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A series of isatin-β-thiosemicarbazones have been designed and evaluated for antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in a plaque reduction assay. Their cytotoxicity was examined using human rhabdomyosarcoma cells (RD cells). Several derivatives of isatin-β-thiosemicarbazone exhibited significant and selective antiviral activity with low cytotoxicity. It was found that the thiourea group at thiosemicarbazone and the NH functionality at isatin were essential for their antiherpetic activity. The synthesis and structure-activity relationship studies are presented.
- Kang, Iou-Jiun,Wang, Li-Wen,Hsu, Tsu-An,Yueh, Andrew,Lee, Chung-Chi,Lee, Yen-Chun,Lee, Ching-Yin,Chao, Yu-Sheng,Shih, Shin-Ru,Chern, Jyh-Haur
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scheme or table
p. 1948 - 1952
(2011/05/04)
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- Synthesis and structure-activity evaluation of isatin-β- thiosemicarbazones with improved selective activity toward multidrug-resistant cells expressing P-glycoprotein
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Cancer multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters presents a significant unresolved clinical challenge. One strategy to resolve MDR is to develop compounds that selectively kill cells overexpressing the efflux transport
- Hall, Matthew D.,Brimacombe, Kyle R.,Varonka, Matthew S.,Pluchino, Kristen M.,Monda, Julie K.,Li, Jiayang,Walsh, Martin J.,Boxer, Matthew B.,Warren, Timothy H.,Fales, Henry M.,Gottesman, Michael M.
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experimental part
p. 5878 - 5889
(2011/10/08)
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- Synthesis and anticonvulsant evaluation of some novel (thio)semicarbazone derivatives of arylalkylimidazole
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A number of novel 2-(1H-imidazole-1-yl)-1-aryl-substituted ethane-1-one N-substituted phenyl(thio)semicarbazones (1-14) were synthesized to test for their anticonvulsant activity against the two seizure models, maximal electroshock (MES) and subcutaneous
- Calis, Uensal,Septioglu, Ebubekir,Aytemir, Mutlu Dilsiz
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experimental part
p. 327 - 334
(2012/02/02)
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- Synthesis and antimalarial activity of novel dihydro-artemisinin derivatives
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The Plasmodium falciparum cysteine protease falcipain-2, one of the most promising targets for antimalarial drug design, plays a key role in parasite survival as a major peptide hydrolase within the hemoglobin degradation pathway. In this work, a series of novel dihydroartemisinin derivatives based on (thio)semicarbazone scaffold were designed and synthesized as potential falcipain-2 inhibitors. The in vitro biological assay indicated that most of the target compounds showed excellent inhibition activity against P. falciparum falcipain-2, with IC50 values in the 0.29-10.63 μM range. Molecular docking studies were performed to investigate the binding affinities and interaction modes for the inhibitors. The preliminary SARs were summarized and could serve as a foundation for further investigation in the development of antimalarial drugs.
- Liu, Yang,Cui, Kunqiang,Lu, Weiqiang,Luo, Wei,Wang, Jian,Huang, Jin,Guo, Chun
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experimental part
p. 4527 - 4538
(2011/08/10)
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- Synthesis, characterization and spectral evaluation of some new substituted thiosemicarbazides and thiosemicarbazones
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A new series of substituted thiosemicarbazides and substituted thiosemicarbazones containing different functional groups, thiosemicarbazones have been synthesized by the condensation reaction between newly synthesized substituted thiosemicarbazides with s
- Pareek, Alok K.,Joseph,Seth, Daya S.
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experimental part
p. 1549 - 1552
(2011/10/12)
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- A series of α-heterocyclic carboxaldehyde thiosemicarbazones inhibit topoisomerase IIα catalytic activity
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A series of novel thiosemicarbazone derivatives bearing condensed heterocyclic carboxaldehyde moieties were designed and synthesized. Among them, TSC24 exhibited broad antiproliferative activity in a panel of human tumor cells and suppressed tumor growth in mice. The mechanism research revealed that TSC24 was not only an iron chelator but also a topoisomerase IIα catalytic inhibitor. Its inhibition on topoisomerase IIα was due to direct interaction with the ATPase domain of topoisomerase IIα which led to the block of ATP hydrolysis. Molecular docking predicted that TSC24 might bind at the ATP binding site, which was confirmed by the competitive inhibition assay. These results about the mechanisms involved in the anticancer activities of thiosemicarbazones will aid in the rational design of novel topoisomerase II-targeted drugs and will provide insights into the discovery and development of novel cancer therapeutics based on the dual activity to chelate iron and to inhibit the catalytic activity of topoisomerase IIα.
- Huang, He,Chen, Qin,Ku, Xin,Meng, Linghua,Lin, Liping,Wang, Xiang,Zhu, Caihua,Wang, Yi,Chen, Zhi,Li, Ming,Jiang, Hualiang,Chen, Kaixian,Ding, Jian,Liu, Hong
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experimental part
p. 3048 - 3064
(2010/09/05)
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- Synthesis, activity, and pharmacophore development for isatin-β- thiosemicarbazones with selective activity toward multidrug-resistant cells
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We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-β- thiosemicarbazones from our initial stud
- Hall, Matthew D.,Salam, Noeris K.,Hellawell, Jennifer L.,Fales, Henry M.,Kensler, Caroline B.,Ludwig, Joseph A.,Szakács, Gergely,Hibbs, David E.,Gottesman, Michael M.
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experimental part
p. 3191 - 3204
(2010/03/31)
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- Synthesis and antituberculosis activity of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives
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New series of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones 3a-t, 1-methyl-5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones 4a-y and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3-thiosemicarbazones 5a-m were synthesized. The structures of the synthesized compounds were confirmed by spectral data and elemental analysis. The new 5-methyl/trifluoromethoxy-1H-indole-2,3-dione derivatives, along with previously synthesized 5-methyl-1H-indole-2,3-dione 3-thiosemicarbazones 6a-l, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. 5-Methyl-1H-indole-2,3-dione 3-thiosemicarbazones (3b, 3d, 3f, 6c, 6d, and 6f), 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones (3q-s) and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3-thiosemicarbazones (5e and 5j-l) were found to be the most potent inhibitors of M. tuberculosis growth described in this study.
- Guezel, Oezlen,Karali, Nilguen,Salman, Aydin
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experimental part
p. 8976 - 8987
(2009/04/11)
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- Synthesis and structure-antituberculosis activity relationship of 1H-indole-2,3-dione derivatives
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New series of 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones 2a-k and 5-fluoro-1-morpholino/piperidinomethyl-1H-indole-2,3-dione-3-thiosemicarbazones 3a-r were synthesized. The structures of the synthesized compounds were confirmed by spectral data, elemental and single crystal X-ray diffraction analysis. The new 5-fluoro-1H-indole-2,3-dione derivatives, along with previously reported 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 2l-v, 1-morpholino/piperidinomethyl-5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 4a-l, and 5-nitro-1H-indole-2,3-dione-3-[(4-oxo-1,3-thiazolidin-2-ylidene)hydrazones] 5a-s, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. Among the tested compounds, 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (2p, 2r, and 2s) and its 1-morpholinomethyl derivatives (4a, 4e, 4g, and 4i) exhibited significant inhibitory activity in the primary screen. The antituberculosis activity of molecules with diverse skeletons was investigated by means of the Electronic-Topological Method (ETM). Ten pharmacophores and ten anti-pharmacophores that have been found by this form the basis of the system capable of predicting the structures of potentially active compounds. The forecasting ability of the system has been tested on structures that differ from those synthesized. The probability of correct identification for active compounds was found as equal to 93% in average. To obtain the algorithmic base for the activity prediction, Artificial Neural Networks were used after the ETM (the so-called combined ETM-ANN method). As the result, only 9 pharmacophores and anti-pharmacophores were chosen as the most important ones for the activity. By this, ANNs classified correctly 94.4%, or 67 compounds from 71.
- Karali, Nilguen,Guersoy, Aysel,Kandemirli, Fatma,Shvets, Nathaly,Kaynak, F. Betuel,Oezbey, Sueheyla,Kovalishyn, Vasyl,Dimoglo, Anatholy
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p. 5888 - 5904
(2008/03/18)
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- Synthesis and antibacterial activity of thiosemicarbazones
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The synthesis of 1-[(2′-hydroxy-4′-isopropoxy-5′- nitrophenyl)-ethanone]-4-(aryl)-3-thiosemicarbazones are carried out by refluxing 4-aryl-3-thiosemicarbazides and 2-hydroxy-4-isopropoxy-5- nitroacetophenone in stoichiometric amounts dissolved in aqueous
- Parekh,Desai
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p. 1072 - 1075
(2007/10/03)
-
- Synthesis and spectral studies of platinum complexes of para-substituted 4-phenylthiosemicarbazides
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Platinum(II) complexes of para-substituted 4-phenylthiosemicarbazides, RPhNHCSNHNH2 (R = H, CH3, Br, F and NO2) have been prepared and characterised by infrared and multinuclear NMR spectroscopy. The thiosemicarbazides act as bidentate ligands bonding through the sulphur and hydrazinic nitrogen atoms to form mixtures of cis- and trans-isomers of square planar complexes. 1H and 195Pt NMR spectroscopy suggest that the trans-isomer predominates in solution and that the relative ratio of trans: cis increases with increasing temperature of synthesis. 15N NMR spectroscopy has also been used to assign the cis- and trans-isomers of platinum complexes of 15N enriched 4-(4′-bromophenyl)thiosemicarbazide using 15N chemical shifts and |1J 195Pt-15N| values. The magnitude of the coupling constant |1J 195Pt-15N| of 238 Hz compares favourably with other platinum(II) complexes in which the 15N donor atom is trans to 15N and thus confirms the assignment of the trans-isomer as the predominant one in solution.
- Arendse, Malcolm J.,Green, Ivan R.,Koch
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p. 1537 - 1545
(2007/10/03)
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