Synthesis, Crystal Structure, Biological Evaluation and in Silico Studies on Novel (E)-1-(Substituted Benzylidene)-4-(3-isopropylphenyl)thiosemicarbazone Derivatives.

A series of (E)-1-(substituted benzylidene)-4-(3-isopropylphenyl)thiosemicarbazone derivatives were synthesized and characterized by FT-IR spectrum, elemental analysis, NMR spectrum, HR-MS spectrum, and X-ray single crystal diffraction technology. The crystal structures and packing of (E)-1-(4-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone and (E)-1-(3-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone were maintained through the intramolecular hydrogen bond (N3-H6⋅⋅⋅N1) and intermolecular hydrogen bonds (N2-H4⋅⋅⋅S1, C14-H14⋅⋅⋅F1 and C7-H7⋅⋅⋅S1). The results obtained by employing the DPPH free radicals scavenging assay indicated that (E)-1-(4-methoxylbenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone had a more significant antioxidant activity compared with other compounds. The results measured by adopting the disc diffusion method elucidated that (E)-1-(4-trifluoromethylbenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone possessed a more prominent antifungal activity than other compounds. Molecular docking showed that (E)-1-(4-chlorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone had the highest affinity with receptor protein (1NMT). Moreover, the drug-likeness characteristic, physicochemical properties, pharmacokinetic profiles, and bioactivity scores of all the compounds were predicted through in silico studies. The results illustrated that (E)-1-(4-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone had the drug-likeness characteristic and all the compounds were considered as moderately biological active molecules.