Synthesis, Biological and Docking Studies of Thiadiazole Amide Derivatives Containing Anthranilic Acid

Document Type : Original Research Articles

Authors
farshid hassanzadeh
elham jafari
mahshid farzan
Hojjat Sadeghi-aliabadi
Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran
10.22059/jsciences.2023.350957.1007765
Abstract
Cancer has been become threatening the health and life of humans. Therefore, attempt to discovery more effective anticancer agents continue. Thiadiazole derivatives have been shown remarkable effects among chemotherapeutic agents. In this study, hybrid molecules containing thiadiazole amide derivatives -aromatic amines (anthranilic acid and 2, 5 dichloro aniline) were synthesized in multi-step reactions including N-amidation  and S-alkylation of thiadiazole. Synthesized compounds were assayed by MTT test against three cell lines. Molecular docking was performed on Src tyrosine kinases. Compounds 5a, 5b and 8 rendered remarkable cytotoxic properties on HeLa with IC50‹ 60 µM. Compound 5b showed significant cytotoxic effect on both cancer cell lines compared to other tested derivatives. Compound 5a with ΔG = -8.05kcal/mol was the best compound among  docked compounds.The results revealed that the quiddity of the amide  substitution  has a definitive role in the cytotoxic activity.
Keywords
Anthranilic acid
Anti cancer
Thiadiazole
Molecular Docking
Subjects
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Journal of Sciences, Islamic Republic of Iran
Volume 34, Issue 2
Spring 2023
Pages 119-127