Synthesis, photophysical and DFT studies of a benzothiadiazole-based bis-Schiff base derivative and its in-silico evaluation as a Sonic Hedgehog protein inhibitor

A novel benzothiadiazole core-based Schiff base (1E,1'E)-1,1'-(benzo[c][1,2,5]thiadiazole-4,7-diylbis(4,1-phenylene))bis(N-(4-(2,2,2-trifluoroethoxy)phenyl)methanimine) KSL-1 was evaluated for its potency to inhibit Sonic Hedgehog protein a potent target to develop anticancer medications through molecular docking studies at two different terminal domains, N & C, with a binding score of −8.4 kcal/mol at the SHH-C terminal domain. Further, the molecular dynamics simulation shows the stable KSL-1 SHH C-terminal domain interactions. The molecular dynamics simulations further revealed that the KSL-1 competitively inhibits the protein splicing activity of the SHH protein, inhibiting the Hedgehog pathway. The structure of the synthesised compound has been established through multinuclear NMR spectral analysis (1H, & 19F). The density functional theory (DFT) analysis utilised to calculate the physicochemical parameters of the synthesised compound, HOMO–LUMO gap (ΔE); a value of 2.9339 eV, suggests that the compound has a high degree of chemical reactivity and a high propensity for charge transfer interactions. Furthermore, KSL-1's high fluorescence, showing UV-absorbance maxima at 330 nm & 410 nm, fluorescence emission spectra with 16 million units of intensity at emission maxima of 470 nm, is investigated for its prominent fluorescent behaviour, showing highly intense blue emission, and CIE coordinates are located.