Synthesis, Biological Evaluation and Molecular Docking of Novel Thiophene‐Based Indole Derivatives as Potential Antibacterial, GST Inhibitor and Apoptotic Anticancer Agents

Heteroaromatic indoles play a leading role in the development of pharmaceutical, medical, chemical and agricultural fields due to their structural properties. In this study, it was first time that biological properties of (antioxidant, antimicrobial, cytotoxic and apoptotis‐induced anticancer) 3‐(5‐bromothiophen‐2‐yl)‐1‐ethyl‐2‐phenyl‐1H‐indole 4 and 3‐([2,2′‐bithiophen]‐5‐yl)‐1‐ethyl‐2‐phenyl‐1H‐indole 5 were described. According to the overall results, while 4 did not show any significant cytotoxic, antioxidant and antimicrobial activities, 5 showed high reducing activity and very strong antibacterial activity against Enterococcus faecalis. Furthermore, 5 showed dose‐dependent cytotoxic effect in all tested cell lines. The EC50 values of the 5 were found to be 16 μM for CaCo‐2, 29 μM for LnCaP, 14 μM for MDA‐MB231, 21 μM for HepG2 and 87 μM for HEK293 cells, respectively. 5 also caused induction of apoptosis and promising glutathione S‐transferase (GST) enzyme inhibition in HepG2 cells. Consequently, 5 could be also considered as a promising medical agent in cancer treatment. 3‐([2,2′‐Bithiophen]‐5‐yl)‐1‐ethyl‐2‐phenyl‐1H‐indole (5) was synthesized by using electrophilic aromatic substation reaction and Pd‐catalyst Stille coupling reactions. It is an active cytotoxic, antioxidant and antibacterial compound. It has also been shown to have an inhibitory effect on glutathione S‐transferases (GST) isozymes and ability to induce apoptosis in liver carcinoma cells (HepG2 cells). In addition, it could be also considered as a promising medical agent in cancer treatment.