ABSTRACT In this study, two chalcone derivatives (E)‐3‐(6‐methoxybenzod1,3dioxol‐5‐yl)‐1‐(3,4,5‐trimethoxyphenyl)prop‐2‐en‐1‐one ( SM3 ) and (E)‐1‐(3,4‐dimethoxyphenyl)‐3‐(6‐methoxybenzod1,3dioxol‐5‐yl)prop‐2‐en‐1‐one ( SM4 ), were designed based on Combretastatin A‐2 and A‐4 and evaluated for anticancer activity against human cervical cancer (SiHa) cells. Both compounds were synthesized via Claisen–Schmidt condensation of a sesamol‐derived aldehyde with substituted aryl ketones in methanolic KOH at room temperature and characterized by 1 H NMR, 1 3 C NMR, IR, and mass spectrometry. Cytotoxicity studies using the MTT assay showed dose‐dependent inhibition, where the compounds exhibited moderate activity, with IC 50 values of 48 µM ( SM3 ) and 41 µM ( SM4 ), using cisplatin as a positive control. Morphological analysis indicated membrane disruption in treated cells, while both compounds showed low toxicity (≥100 µM) toward the HEK cell line. DFT calculations (B3LYP/6‐311G(d,p)) revealed higher chemical reactivity for SM3 due to its lower HOMO–LUMO gap, whereas Natural Bond Orbital (NBO) analysis suggested greater charge delocalization in SM4, correlating with its relatively better biological performance. Molecular docking against tubulin (PDB ID: 1SA0) showed strong binding affinities for SM3 (−8.091 kcal/mol) and SM4 (−8.007 kcal/mol). ADME analysis indicated favorable drug‐like properties. Overall, SM3 and SM4 represent promising scaffolds for further development as microtubule‐targeting anticancer agents.
Gautam et al. (Wed,) studied this question.