Synthesis, biological evaluation, and molecular docking studies of substituted chromone-2-carboxamide derivatives as anti-breast cancer agents

Abstract Breast cancer is the second leading cause of mortality among women, accounting for 12.5% of all new cancer cases worldwide. By 2030, the estimated number of deaths will escalate to 11.4 million. The research objective is to design and synthesize safe and effective anti-breast cancer agents. A series of substituted chromone-2-carboxamide derivatives ( 5a–n ) were synthesized in moderate to high yields. These compounds’ ( 5a–n) antiproliferative activity was evaluated against human ER(+) MCF-7 (breast), ER(−) MDA-MB-231 (breast), and Ishikawa (endometrial) cancer cell lines using CellTiter-Glo assay at concentrations ranging from 0.01 to 100,000 nM. Seven compounds showed significant cytotoxicity against at least one cancer cell line with an IC 50 value of 25.7–87.8 µM. Compound 5g showed high activity on MCF-7 (IC 50 = 25.7 µM), MDA-MB-231 (IC 50 = 48.3 µM), and Ishikawa (IC 50 = 25.7 µM) cell lines. The newly synthesized molecules were docked in the active sites of the human estrogen receptors (ERs), ER-α (7KBS), and ER-β (2FSZ) crystal structures to determine the locations of the active compounds’ probable binding sites (bioactive conformations).