Microwave-assisted green synthesis and anti-proliferative evaluation of novel chromene-1,2,4-oxadiazole hybrid analogues as potential anticancer agents targeting MCF-7 cell lines

Abstract

Objectives: Breast cancer remains a leading cause of cancer-related mortality worldwide, with existing therapies limited by resistance and toxicity. This study aimed to design, synthesize, and evaluate novel chromene-1,2,4-oxadiazole hybrid derivatives as potential EGFR-targeted anticancer agents against MCF-7 breast cancer cells. Methods: Ten hybrid derivatives (CHO1-CHO10) were synthesized by two-step microwave-assisted green synthesis by the strategy of cyclodehydration. All compounds were characterised through FT-IR, 1H NMR and ESI-MS; drug likeliness was analysed by Lipinski's Rule of Five and Veber's rules using ForceADME, toxicity screening was done using GeinTox-II and molecular docking was performed using GeinDock Suite v2.5.6.0 against EGFR tyrosine kinase (pdb: 1XKK). Selected compounds were tested in vitro for antiproliferative activity against MCF-7 cells by MTT assay. Results: All the compounds selected were found to be drug like with a molecular weight in the range of 377.37-459.43 g/mol and bioavailability score of 0.85. CHO4 was removed because of the predicted carcinogenicity and mutagenicity. The docking score was in between −9.582 and −10.74 kcal/mol, which dock of CHO5 showed high affinity −10.74 kcal/mol than lapatinib (−11.24 kcal/mol). MTT assay revealed CHO5 as the most potent compound (IC₅₀ 7.84 ± 0.23 µM), followed by CHO9 (9.12 ± 0.31 µM) and CHO2 (11.47 ± 0.38 µM). Conclusion: CHO5 demonstrated promising EGFR inhibitory potential with favorable drug-likeness and acceptable safety profile, positioning chromene-oxadiazole hybrids as clinically translatable anticancer candidates warranting further in vivo validation and mechanistic apoptosis studies.