Indole‐Chalcone‐Sulfonamide Hybrids: Synthesis and Dual Biological Evaluation as Anticancer and Antioxidant Agents

OpenAlex · İngilizce

ABSTRACT 3‐(1 H ‐indol‐3‐yl)‐1‐(4‐substitutedphenyl)prop‐2‐en‐1‐one derivatives ( 2a–i ) and 2‐[3‐[3‐(3‐oxo‐3‐substitutedphenylprop‐1‐en‐1‐yl)‐1 H ‐indol‐1‐yl]‐N‐(4‐sulfamoylphenyl)acetamide compounds ( CS1 – CS9) were designed and synthesized. The imidazole‐derived original intermediate 2f showed greater effectiveness against the C6 rat glioma cell line. The compound CS1 and the original intermediates 2h , 2g , and 2i were the only other derivatives that showed substantial cytotoxic activity when compared to the reference drug tofacitinib. Among them, 2g , 2i , and 2h exhibited superior cytotoxic activity against the A549 lung cancer cell line. Compound 2f demonstrated cytotoxic effects on the C6 cancer cell line at 5 times the concentration of cisplatin and 20 times that of tofacitinib. Its selective cytotoxic effect on normal cells was also demonstrated at a concentration that was almost 66 times higher than that of the cancer line. Notably, the original chalcones ( 2f–2i ) exhibited greater cytotoxic activity than the final compounds ( CS1 – CS9 ). The IC 50 values of the compounds ranged from 0.103 to 1.375 mM. The most promising compound, 2f , exhibited drug‐likeness characteristics consistent with standard drug‐likeness parameters. Compound 2f , 1‐(4‐(1 H ‐imidazol‐1‐yl)phenyl)‐3‐(1 H ‐indol‐3‐yl)prop‐2‐en‐1‐one, might be regarded as a potent and selective lead compound for the next drug design investigations.