Molecular modelling and cytotoxic activity of donor-π-acceptor fluorescent diphenylamino-thiazole chromophores

Abstract Three chromophores 5a-c based on the diphenylamine (donor), thiazole (π-core) and acrylonitrile (acceptor) were synthesized and characterized by IR, NMR, MS analyses. The donor–acceptor chromophores 5a-c were studied by spectroscopy and TD-DFT. The nitro-substituted probe 5a showed the smallest FMO energy gap (4.97 eV), largest solvatochromic red shift (34 nm), and most red-shifted emission (613 nm), while the cyano analogue 5b exhibited the highest fluorescence efficiency ( $$\phi$$ ϕ = 0.75). These results demonstrate how terminal acceptor groups effectively tune ICT strength and optical performance. Besides, the in vitro cytotoxicity of chromophores 5a-c against three human cancer cell lines has been investigated, where 5b showed intense cytotoxicity towards HT‐29 colon cancer cells (IC50 = 21.05 ± 0.12 µM) with better selectivity than that of doxorubicin. In addition, the in vitro anti‐VEGFR‐2 kinase inhibitory activity against model drug sorafenib indicated that the chromophores were found to possess micromolar to sub-micromolar potency, especially, 5a exhibited the strongest inhibitory activity (IC50 = 0.44 ± 0.16 µM). However, a molecular docking study was performed to discover their binding affinities against the crystal structure of the kinase receptor (PDB: 1YWN) employing molecular docking simulations. The chromophores’ binding free energies have been recorded in the proper range from -6.10 to -6.59 kcal/mol, comparable to that of the reference drug sorafenib (-6.24 kcal/mol). Graphical Abstract