Design and Synthesis of Isatin‐1,2,3‐triazole Hybrids as Anticancer Agents

Abstract Isatin, a chemically defined indole‐1 H ‐2,3‐dione, is widely considered a desirable therapeutic fragment in the field of drug discovery. Similarly, the 1,2,3‐triazole ring is a major pharmacophore system among nitrogen containing heterocycles. Molecular hybrids comprising isatin and acyl azides functions linked by triazole rings were synthesized and tested for cytotoxic effects against sixty human cancer cell lines due to the drug resistance with most of the currently utilized anticancer medicines. The 1,2,3‐triazole‐isatin hybrids (8a–8j) were produced in high yields and with exceptional purity via Huisgen's 1,3‐dipolar cycloaddition involving acyl azide, 7a–7j , and an Isatin‐based N ‐alkyne 3 in the presence of water as the principal solvent and n ‐Bu‐OH and DMF as cosolvents. compounds 8c , 8g , and 8h showed highly effective growth inhibition against breast, leukemia, and melanoma cell lines, with mortality ranging from 6% to 99% and PGI = >70% in the majority of instances. While 8a and 8b showed weak to moderate action against all the tested cancer cell line and few compounds 8d , 8f , 8i, and 8j shows low activity. A molecular docking study against cyclin‐dependent kinase (CDK2) could provide insights into the mechanistic basis of antitumor activity.