A thiosemicarbazone derivative as a potential multi-target inhibitor: Molecular docking, DFT, QTAIM, and NLO investigation of thione and thiol tautomers.

Thiosemicarbazones have been widely used due to their various biological activities and interesting NLO behavior. In this study, the thione and thiol tautomers of [(E)-1-[4-[(2,4-dihydroxyphenyl) diazenyl] phenyl] ethylideneamino] thiourea have been studied at the DFT level of theory using BVP86/6-311G(d,p), coupled with molecular docking against tyrosinase, BRAF, and MEK1. The thione tautomer displayed a smaller HOMO-LUMO gap (1.780 eV), greater electrophilicity (9.52 eV), and enhanced NLO characteristics (static β = 134.525 × 10-30 esu, dynamic β = 3192.119 × 10-30 esu), along with enhanced binding affinity towards TYRP1 (-8.1 kcal/mol), and inhibitory activity against BRAF (Kᵢ = 0.214 μM), and MEK1 (Kᵢ = 0.497 μM). Based on these results, it is evident that the thione tautomer is a suitable candidate for development as a dual-inhibitor of the tyrosinase/kinase pathways, which can be used for melanoma treatment and also for optoelectronic applications. This work provides the link between theoretical predictions and experimental drug design and forms the basis for future syntheses of thiosemicarbazone-based drugs.