Synthesis, docking and cytotoxicity evaluation of N-(5-(benzyl-thio)-1,3,4-thiadiazol-2-yl)-2-(3-methoxyphenyl)acetamide derivatives as tyrosine kinase inhibitors with potential anticancer activity

Ahmad Mohammadi-Farani; Tayebeh Bahrami; Alireza Aliabadi

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RESEARCH ARTICLE

Year : 2014 | Volume : 3 | Issue : 2 | Page : 159-168

Synthesis, docking and cytotoxicity evaluation of N-(5-(benzyl-thio)-1,3,4-thiadiazol-2-yl)-2-(3-methoxyphenyl)acetamide derivatives as tyrosine kinase inhibitors with potential anticancer activity

Ahmad Mohammadi-Farani¹, Tayebeh Bahrami², Alireza Aliabadi³
¹ Novel Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences; Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
² Students Research Committee, Kermanshah University of Medical Sciences; Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
³ Novel Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences; Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

Correspondence Address:
Alireza Aliabadi
Novel Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences; Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah
Iran

Source of Support: None, Conflict of Interest: None

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In the recent years, targeted therapy of the neoplastic diseases is a current strategy used by oncologists. Hence, design and discovery of novel targeted anticancer therapeutics is an interesting topic in the current research of medicinal chemistry. A new series of 1,3,4-thiadiazole derivatives were prepared and their anticancer activity was assessed against PC3, SKNMC and HT29 cell lines by application of the MTT assay. Compound 3e with para positioning of the methoxy moiety demonstrated the highest inhibitory potency against PC3 (IC₅₀ = 22.19 ± 2.1 μM) and SKNMC (IC₅₀ = 5.41 ± 0.35 μM) cell lines in this series. This compound rendered a superior cytotoxic activity than imatinib. Compound 3f with ortho positioning of the fluorine displayed the most cytotoxic activity against HT29 cell line compared to other tested derivatives (IC₅₀ = 12.57 ± 0.6 μM). Molecular docking studies on Abl as well as Src tyrosine kinases were also performed and potential hydrogen bindings were observed for ligand-receptor interaction.

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