Facile green diversity-oriented synthesis, molecular docking, and cytotoxicity evaluation of quinoline -triazole appended peptidomimetics as inhibitors of human breast cancer cell line MCF-7

Abstract

The synthesis of quinoline-based drugs has significant interest from researchers due to their broad spectrum of biological activities. In this context, a concise approach for the synthesis of quinoline-functionalized hybrid peptidomimetics is described. The peptidomimetics are constructed based on a recombinant approach via Iqbal multicomponent coupling strategy and click chemistry and were linked via copper (I) catalysed [3 + 2] azide-alkyne cycloaddition. The peptidomimetics showed exceptional inhibitory properties for CDK2 protein which is responsible for many malignancies and also showed remarkable cytotoxicity against human breast cancer cell line MCF-7. The IC₅₀ value (8 μM) and binding affinity (−10.2 Kcal/mol) found for 4b against MCF-7 cells are hopeful for the development of potential anticancer drugs based on these new scaffolds.