Synthesis, characterization, antimicrobial, antioxidant, and molecular docking study of 3-(2,5-dichlorothiophen-3-yl)-5-arylpyrazole-1-carbothioamides and their thiazole derivatives

In the present study, a new series of 3-(2,5-dichlorothiophen-3-yl)-5-aryl-4,5-dihydro-1 H -pyrazole-1-carbothioamides 2 were synthesized either by the reaction of ( E )-3-aryl-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-ones 1 with thiosemicarbazide or by one-pot reaction of 3-acetyl-2,5-dichlorothiophene with the corresponding aldehyde and thiosemicarbazide. Additionally, 2-(3-(2,5-dichlorothiophen-3-yl)-5-aryl-4,5-dihydro-1 H -pyrazol-1-yl)-4-phenylthiazoles 3 were synthesized in 46–89% yields by the reflux of carbothioamides 2 with 2-bromoacetophenone. The structures of the newly synthesized compounds were characterized by IR, 1 H-NMR, 13 C-NMR, DEPT-135, and mass spectrometry analysis (MS). All new compounds were evaluated as antimicrobial and antioxidants. Compound ( 3b) exhibited moderate activity against Bacillus subtilis and Penicillium fimorum , 14 ± 0.5 mm and 18 ± 0.75 mm, respectively, while the other synthesized compounds did not show activity against the tested microbes. The most potent antioxidant activity showed by compound ( 2a) and ( 2e ) with 95.2% and 96.3%, which considered good to excellent antioxidant activity compared with the control (ascorbic acid) and other synthesized compounds. Molecular docking study of the new compounds with cytochrome P450 14 alpha-sterol demethylase (CYP51) was carried out to evaluate their possibility as drugs and to implement structural improvements for this purpose. All synthesized compounds exhibited good affinity with (CYP51), notably, ( 3a ) and ( 3b ) compounds showed the highest affinity with the lowest binding energies. Graphical abstract