Acta Pharm. 70 (2020) 499-513

full paper

Original research paper

Synthesis and biological evaluation of novel 1,3,4-thiadiazole derivatives as possible anticancer agents

ULVIYE ACAR ÇEVIK, DERYA OSMANIYE, SERKAN LEVENT, BEGÜM NURPELIN SAĞLIK,BETÜL KAYA ÇAVUŞOĞLU, ABDULLAH BURAK KARADUMAN, YUSUF ÖZKAY and ZAFER ASIM KAPLANCIKLI

uacar@anadolu.edu.tr

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

² Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

³ Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

Accepted November 19, 2019

Published online December 16, 2019

The synthesis of new N-(5-substituted-1,3,4-thiadiazol-2-yl)-2-[(5-(substituted amino)-1,3,4-thiadiazol-2-yl)thio]acetamide derivatives and investigation of their anticancer activities were the aims of this work. All the new compounds’ structures were elucidated by elemental analyses, IR, ¹H NMR, ¹³C NMR and MS spectral data. Anticancer activity studies of the compounds were evaluated against MCF-7 and A549 tumor cell lines. In addition, with the purpose of determining the selectivity of cytotoxic activities, the most active compound was screened against a healthy NIH3T3 cell line (mouse embryonic fibroblast cells). Among the tested compounds, compound 4y (N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-((5-(p-tolylamino)-1,3,4-thiadiazol-2-yl)thio)acetamide), showed promising cytotoxic activity against MCF7 cancer cell with an IC₅₀ value of 0.084 ± 0.020 mmol L^–1 and against A549 cancer cell with IC₅₀ value of 0.034 ± 0.008 mmol L^–1, compared with cisplatin. The aromatase inhibitory activity was evaluated for compound 4y on MCF-7 cell line showing promising activity with IC₅₀ of 0.062 ± 0.004 mmol L^–1.

Keywords: 1,3,4-thiadiazole, anticancer activity, aromatase inhibitory activity, MTT assay