Rational Design of Diphenylamino-Thiazole Donor-π-Acceptor Schiff Base Chromophores: Solvatochromic Fluorescence, TD-DFT Insights, and Cytotoxic Activity

Three diphenylamino-thiazole donor-π-acceptor Schiff-base chromophores 5a-5c were designed and synthesized to explore their photophysical properties and anticancer potential. The synthesized structures were characterized by FTIR and 1H/13C NMR, and mass spectrometry. UV-Vis studies revealed pronounced positive solvatochromism (λmax = 406–470 nm), consistent with efficient intramolecular charge transfer, and supported by density functional theory calculations. The chromophores exhibited strong visible emission (529–594 nm) with large Stokes shifts (≈ 4.3–5.6 × 103 cm− 1), indicating important excited-state relaxation. Kamlet-Taft analysis identified solvent dipolarity/polarizability and hydrogen-bond acceptor ability as dominant factors governing solvatochromism (R2 = 0.977–0.983). Time-dependent density functional theory calculations reproduced the experimental spectra, confirming HOMO→LUMO π→π* Intramolecular Charge Transfer transitions and effective donor-acceptor electronic communication. Cytotoxic evaluation revealed against HT-29, MCF-7, and HepG2 cell lines, with chromophore 5b showing the highest potency (IC50 = 11.30 ± 0.61–16.46 ± 0.37 µM), comparable to Sorafenib, while maintaining low toxicity toward WI-38 normal cells, indicating acceptable selectivity. Molecular docking revealed moderate binding affinities, particularly for chromophore 5a (S = -7.05 kcal/mol), surpassing the reference drug and suggesting a preliminary inhibitory scaffold. Moreover, in silico pharmacokinetic analysis indicated acceptable drug-likeness, with satisfactory molecular weight, lipophilicity (LogP ≈ 4.0-4.7), TPSA (50.9–96.8 Å2), and good predicted oral bioavailability. Overall, these in vitro findings identify diphenylamino-thiazole chromophores, particularly 5b and 5a, as promising candidates for further development as preclinical investigation with integrated optoelectronic functionality.