An efficient protocol for the synthesis, biological screening and molecular docking studies of 3,4-dihydropyrimidine-2-one/thione derivatives

Introduction: Heterocyclic compounds are vital to life, since they constitute the most interesting part of the pharmacologically active drugs. Dihydropyrimidine-2-one/thione (DHPM) as the heterocyclic nucleus is the basic part of the most natural as well as synthetic drugs. Synthesis of new derivatives of DHPM and screening their pharmacological potential appear to be an important goal. Methodology: In this study, we have synthesized 15 derivatives of 3,4-dihydropyrimidin-2(1H)-ones/thiones through simple one-step synthetic method comprising one-pot condensation of variously substituted benzaldehydes, urea/thiourea and ethyl acetoacetate using ammonium chloride in methanol as well as under solvent-free conditions. In comparison, the former methodology was proved more efficient, convenient and gave higher yields. Moreover, those compounds were screened for their potential against bacterial strains (S. aureus and E. coli) and fungal strains (C. albicans and C. parapsilosis). Results and Discussion: The experimental results revealed that the synthesized compounds are more active against C. albicans fungus as compared to other tested microbes. Amongst all the synthesized derivatives, compound 3 showed significant non-competitive potential antifungal activity in vitro antimicrobial assay. Theoretically, molecular docking studies showed that these compounds can bind effectively to oxidoreductase enzyme of E. coli and CYP-51 oxidoreductase of C. albicans. Conclusion: Herein, we report improved and high yield reaction conditions for the synthesis of biologically active dihydropyrimidine-2-one, and-thione derivatives. Remarkably, most of the synthesized compounds demonstrated moderate to very good antifungal activity in comparison to the antibacterial activity.