Design, synthesis and biological screening of novel heterocyclic ring derivatives as antibacterial agents

Abstract

For a long time, numerous attempts are being made by researchers to discover and develop new antimicrobial agents based on synthetic compounds and medicinal plants. These attempts were forced due to increasing rate of microbial resistance. In the present study, it has been discussed that the synthesis of various dihydropyrimidine fused with benzimidazole moiety. In which o-phenylenediamine and chloroacetic acid react in acidic medium by nucleophilic addition reaction to form 2-chloro methyl Benzimidazole. (1). The substituted Chalcone (2) was synthesized by a claisan-schmidt condensation reaction. The condensation of an aromatic aldehyde with aromatic ketone having α- hydrogen in presence of a strong base to form α,β-unsaturated ketone i.e Chalcone is form. The substituted Chalcone react with thiourea by Michael reaction. It is also called 1,4 addition reaction. In which thiourea act as nucleophile attack on 4-positon of the α,β-unsaturated ketone and keto-enol tautomerism occurs and 4- substitutedphenyl-6-substitutedphenyl-4,5-dihydropyrimidine-2- thiol . (3). Benzimidazole (1) fused with substituted dihydropyrimidine-2-thiol (3) in presence of THF and form 2-((4-substituted phenyl-6-substituted phenyl pyrimidine-2-ylthio)methyl)-1H-benzo[d]imidazole. (4). The synthesized compounds APUS1 – APUS21 were assigned by its spectral data (IR, NMR and mass spectra). The synthesized compounds have been tested for their antibacterial activity against Gram (+) bacteria (S. aureus) , (B.subtilis) and Gram (-) bacteria (E.coli ) by agar diffusion method. Compound having electron withdrawing group show significant activity and having electron donor group show moderate activity. Keywords: Antibacterial activity, Molecular docking, Dihydropyrimidine, Benzimidazole.