Facile synthesis of pyrimidine substituted-1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole derivatives and their antimicrobial activity correlated with molecular docking studies.

• A variety of pyrimidinyl oxa/thia/triazoles are prepared using trimethylsilyl isothiocyanate. • Docking results indicated that the compounds 3e, 5e, 7a have better docking scores than Chloramphenicol. • The compounds 3e, 5a, 5e have better docking scores than Fluconazole. • The unsubstituted, methyl and nitro substituted molecules showed greater antimicrobial activity. Organosilicon reagent-trimethylsilyl isothiocyanate, a common reagent for the development of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles was reported by the reaction with heteroaromatic acid hydrazides under conventional and ultrasonication methodologies in a polar protic solvent, ethanol under appropriate conditions. Molecular docking studies were performed with the X-ray crystal structures of the target molecules (PDB ID: 2w9s and PDB ID: 6f0e). The docking results indicated that H-bond interactions and hydrophobic interactions were responsible for the inhibition of protein. All 15 synthesized molecules showed excellent binding energy than the standard drugs. The compounds 3a, 3b, 3e, 5a, 5b, 5e and 7a exhibited low MIC values against S. aureus whereas 3a, 3b, 5a, 5b and 7a against B. subtilis. The compounds 5a, and 5b also displayed low MIC values against P. aeruginosa. The MBC of these compounds is 2×MIC, and is equal to standard drug, Chloramphenicol. The compounds 3a, 3b, 3e, 5a, 5b, 5d and 5e showed low MIC values against A. niger whereas 3a, 5a, 5b, 7a, 7b and 7e against P. Chrysogenum. The MFC is 2×MIC and is equal to standard drug, Fluconazole. The structure-activity relationship of the compounds revealed that unsubstituted, methyl and nitro substituted compounds showed greater antimicrobial activity than those with chloro and bromo substituents. [Display omitted] [Display omitted] [ABSTRACT FROM AUTHOR]