Abstract

Flavanones represent an important class of naturally inspired scaffolds with diverse pharmacological activities, including notable anticancer potential. Structural modification of the flavanone core offers opportunities to enhance biological performance and identify new lead molecules. In the present study, a series of nine flavanone-arylhydrazone derivatives was synthesised through the condensation of substituted flavanones with corresponding phenylhydrazines under reflux conditions. The synthesised compounds were obtained in good yields and were structurally confirmed using infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectrometry, which collectively verified the integrity of the hydrazone linkage and aromatic substitutions. The derivatives were evaluated for in vitro cytotoxicity against two human breast cancer cell lines, michigan cancer foundation-7 (hormone-dependent) and MDA-MB-231 (triple-negative), using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tamoxifen served as the reference standard. All compounds exhibited dose-dependent cytotoxicity, with variable responses across both cell lines. Among them, compounds 3 and 1 demonstrated the highest activity, with IC50 values of 33.54±2.2 µM and 36.60±2.4 µM in Michigan cancer foundation-7 cells and 41.08±2.6 µM and 44.21±2.7 µM in MDA-MB-231 cells, respectively. Structure-activity analysis indicated that derivatives bearing electron-withdrawing substituents, such as nitro and halogens, displayed comparatively enhanced potency. The findings emphasise the possible use of flavanone–arylyhydrazone hybrids as promising anticancer candidates. Compounds 3 and 1, in particular, may serve as lead molecules for further mechanistic investigations and optimisation studies aimed at developing new therapeutic agents for breast cancer.