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

Abstract

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.

Synthesis, Characterization, Antibacterial and Antifungal Activities Evaluation of Metal Complexes With Benzaldehyde‐4‐methylthiosemicarbazone Derivatives

“…[8] These properties make metal complexes good candidates with biological properties such as effective antimicrobial agents. [9] Specifically, transition metal complexes of thiosemicarbazone derivatives were extensively studied because of their numerous biological activities [10] against malarial, [11][12][13] bacterial, [14] fungal infections, [15][16][17] in addition to their antitumor activity against various cancer cell lines. [18][19][20][21][22][23] Substituted benzaldehyde N(4)-thiosemicarbazones with functional group attached at meta and para position on the aromatic ring and, an alkyl group at the terminal N4 nitrogen atom and the presence of a functional binding site, [6,24,18] made them the subjects of broad investigation because of their properties as herbicides, insecticides and plant growth regulators.…”

Study on the synthesis and theoretical calculation of a chlorine‐substituted thiosemicarbazone derivative

“…[21,22] In recent years, this research group has mainly conducted systematic research on thiosemicarbazone, and a series of halogen-substituted thiosemicarbazone and its derivatives have been synthesized, such as (E)-N-(4-ethylphenyl)-2-(4-fluorobenzylidene)thiosemicarbazone, (E)-N-(3-isopropylphenyl)-2-(substituted benzy-lidene) thiosemicarbazone and (E)-N-(3,5-dimethylphenyl)-2-(3-fluorobenzylidene)thiosemicarbazone. [23][24][25] By comparing the synthesized halogen-substituted thiosemicarbazone with other group-substituted thiosemicarbazone, and it was found that the former generally has stronger antifungal activity and ideal physical and chemical properties than the latter.…”