Synthesis, Cytotoxic Evaluation, Docking and QSAR Study of N-(4-Oxo- 2-(4-((5-Aryl-1,3,4-Thiadiazol-2-yl)Amino)Phenyl)Thiazolidin-3-yl) Benzamides as Antitubulin Agents

Author(s): Chawla Amit, Chawla Payal, U.S. Baghel, Deep Aakash

Journal Name: Current Topics in Medicinal Chemistry

Volume 16 , Issue 22 , 2016

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Graphical Abstract:


In the present study an efficient strategy for the synthesis of thiazole and thiadiazole derivatives was developed and clubbed together both of the substituted nucleus to form the analogues of combretastatin A-4 (tubulin polymerization inhibitors.). Synthesis was started by the reaction of substituted benzoic acid with thionyl chloride followed by the reaction with hydrazine, p-chloro benzaldehyde and thioglycolic acid to form substituted thiazole derivatives. On the other side hydrazides were reacted with ammonium thiocyanate and strong acid to form substituted thiadiazole compounds. Finally thiazole and thiadiazole compounds were clubbed with the help of dioxan and triethylamine. All novel derivatives (TH01-TH40) were screened for their cytotoxicity activity using MTT assay against three cancer cell lines viz. A-549 (lung carcinoma), HT-29 (colon carcinoma), HeLa (cervix carcinoma). Compounds TH08 exhibited highest activity, due to the presence of trimethoxy substitution on phenyl ring. In QSAR study these results were correlated with physicochemical parameters and the correlation of XlogP, kaapa2, Quadrupole1 with cytotoxic activity on A-549 (lung carcinoma) was found highest (r2: 0.941; F: 99.103; Se: 0.0006). In docking study binding of active molecule (TH08) was found very well with α, β tubulin (PDB: 1SA0) protein.

Keywords: Thiazole, Combretastatin A-4, Thiadiazole, Cytotoxicity, QSAR, MTT, Docking.

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Article Details

Year: 2016
Published on: 29 June, 2016
Page: [2509 - 2520]
Pages: 12
DOI: 10.2174/1568026616666160212124316
Price: $65

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