Synthesis of novel benzimidazole–oxadiazole derivatives as potent anticancer activity

• Published in: Medicinal chemistry research Vol. 28; no. 12; pp. 2252 - 2261
• Main Authors: Çevik, Ulviye Acar, Osmaniye, Derya, Çavuşoğlu, Betül Kaya, Sağlik, Begüm Nurpelin, Levent, Serkan, Ilgin, Sinem, Can, Nafiz Öncü, Özkay, Yusuf, Kaplancikli, Zafer Asım
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2019; Springer Nature B.V
• Subjects: 60 APPLIED LIFE SCIENCES; Adenocarcinoma; Annexin V; Anticancer properties; Antitumor activity; Antitumor agents; APOPTOSIS; BENZIMIDAZOLES; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer; CARBON 13; CARCINOMAS; Cell Biology; Cell death; Cellular structure; Cisplatin; Cytotoxicity; Deoxyribonucleic acid; Derivatives; DNA; DNA structure; DNA topoisomerase; Electrophoresis; Embryo fibroblasts; ENZYMES; FIBROBLASTS; Gel electrophoresis; Hepatocytes; HYDROGEN 1; LIVER; Liver cancer; Mass spectroscopy; MICE; NMR; NUCLEAR MAGNETIC RESONANCE; Original Research; OXADIAZOLES; Pharmacology/Toxicology; Toxicity; TRIOCTYLPHOSPHINE OXIDE; Tumor cell lines; DNA flow cytometric; 1,3,4-Oxadiazole; Anticancer; 2D NMR; Benzimidazole
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-019-02451-0

DNA topoisomerase I regulates DNA topological structure in many cellular metabolic processes and is a validated target for the development of antitumor agents. In this work, a series of novel 2-[(5-(4-(5(6)-substituted-1 H -benzimidazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)thio]-1-(4-substitutedphenyl)ethan-1-ones ( 4a–4s ) derivatives have been synthesized and evaluated for DNA Topo I inhibition and cytotoxicity. The structures of the compounds ( 4a–4s ) were confirmed by IR, 1 H-NMR, 13 C-NMR, 2D NMR, and mass spectroscopy. Anticancer activity of these compounds was assessed against two different human cancer cell lines A549 (human lung adenocarcinoma) and HepG2 (human liver cancer cell line), as well as normal mouse embryonic fibroblast cells (NIH3T3). IC 50 values of compounds 4a , 4c , and 4 f were highest than those exhibited for the reference drug cisplatin. Then, the inhibitory effect of 4a , 4c , and 4 f compounds on topoisomerase I enzyme with the relaxation assay was investigated on supercoiled DNA using agarose gel electrophoresis. The Annexin V-FITC assay demonstrated that these compounds induce cell death by apoptosis.