Synthesis, antimicrobial studies, and molecular docking of some new dihydro-1,3,4-thiadiazole and pyrazole derivatives derived from dithiocarbazates

A series of 3-acetyl-2-aryl-5-methylthio-2,3-dihydro-1,3,4-thiadiazoles 3a–g, N- (4-acetyl-5-aryl-4,5-dihydro-1,3,4-thiadiazol-2-yl) acetamide derivatives 5a–e and spiro-compound 7 was prepared from starting material dithiocarbazates using N-methylpyrrolidone (NMP) /acetic anhydride mixture. Furthermore, a new series of 5-amino-3- (methylthio) -1-substituted-1H-pyrazole-4-carbonitrile derivatives 12a–d was prepared using two synthetic routes: (i) via reaction of bis (methylthio) methylene malononitrile 8 with carbothiohydrazides 11a–d, or (ii) via reaction of methyl 5-amino-4-cyano-3- (methylthio) -1H-pyrazole-1-carbodithioate 9a with primary/secondary amines. The antimicrobial screening of newly synthesized compounds revealed that compounds 3b, 7, and 12d are the most potent against the Gram-positive (S. aureus) and the Gram-negative (E. coli) bacteria compared to ciprofloxacin as reference drug. Mechanistically, the theoretical docking results of 3b, 7 and 12d suggested that they may act as potent inhibitors of theDNA gyrase.