Synthesis, characterization, cytotoxic investigation of curcumin-based 4-phenylchromene derivatives and study of DNA interaction using experimental and computational methods

Abstract

Curcumin exhibits a distinctive anti-proliferative effect on various malignant tumors. However, its limitations, such as low bioavailability and poor aqueous solubility, have led to the development of different curcumin analogs. In this study, thirteen curcumin-based 4-phenylchromene compounds were synthesized as ligands through nucleophilic additions involving curcumin, 3-dimethylaminophenol, and various aryl aldehydes. The structures of these synthesized compounds were verified using FT-IR, ¹H NMR, ¹³C NMR, and MASS spectral data. Their cytotoxic effects were assessed using the MTT assay on A2780 (ovarian cancer) and Hela (cervical cancer) cell lines. Additionally, FT-IR, fluorescence, UV–vis spectroscopy, and molecular modeling studies were conducted to investigate the interaction between selected ligands and calf-thymus DNA. Among the compounds, L3 emerged as the most toxic ligand, with an IC₅₀ ranging from 4 to 4.5 µg/mL, and was found to bind to CT-DNA in a groove-binding mode with a binding constant of 3.98 × 10³ M⁻¹.