Indazole–Pyridine Hybrids: Design, Synthesis, and Biological Evaluation as Possible Anticancer Agents against Breast Cancer Cell Lines

A novel series of (3-amino-5-methyl-1H-indazol-1-yl)(5-substituted-pyridin-3-yl)methanone derivatives (7a–7j) was synthesized and structurally confirmed using IR, NMR, and mass spectrometry. Molecular docking analysis performed with AutoDock identified compound 7c as the most potent binder (–8.7 kcal/mol), surpassing the standard drug Entrectinib. Compounds 7i and 7e also demonstrated favorable interactions, suggesting their potential as lead molecules. Predicted ADME features include high gastrointestinal absorption and minimal inhibition of cytochrome P450 enzymes, leading to good oral availability. In vitro cytotoxicity tests on MCF-7 breast cancer cells demonstrated that compounds 7b and 7c produced strong antiproliferative effects, with 7c achieving up to 64% reduction in cell viability, approaching the efficacy of Adriamycin. Moderate activity was observed in compounds 7d, 7g, and 7i, whereas 7a, 7e, and 7f displayed weak activity. Overall, compounds 7b and 7c emerge as promising candidates for further optimization, with structural elements such as cyclopentyl and halogen substituents contributing significantly to their biological activity. These results provide a foundation for mechanistic exploration and development of new anticancer agents.