Abstract
2-azido-1H-benzo[d]imidazole derivatives 1a,b were reacted with a β-ketoester such as acetylacetone in the presence of sodium ethoxide to obtain the desired molecules 2a,b. The latter acted as a key molecule for the synthesis of new carbazone derivatives 4a,b that were submitted to react with 2-oxo-N-phenyl-2-(phenylamino)acetohydrazonoyl chloride to obtain the target thiadiazole derivatives 6a,b. The structures of the newly synthesized compounds were inferred from correct spectral and microanalytical data. Moreover, the newly prepared compounds were subjected to molecular docking studies with DNA gyrase B and exhibited binding energy that extended from −9.8 to −6.4 kcal/mol, which confirmed their excellent potency. The compounds 6a,b were found to be with the minimum binding energy (−9.7 and −9.8 kcal/mol) as compared to the standard drug ciprofloxacin (−7.4 kcal/mol) against the target enzyme DNA gyrase B. In addition, the newly synthesized compounds were also examined and screened for their in vitro antimicrobial activity against pathogenic microorganisms Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, Aspergillus niger, and Candida albicans. Among the newly synthesized molecules, significant antimicrobial activity against all the tested microorganisms was obtained for the compounds 6a,b. The in silico and in vitro findings showed that compounds 6a,b were the most active against bacterial strains, and could serve as potential antimicrobial agents.
Highlights
IntroductionNitrogen-containing heterocyclic analogues have received great interest in drug discovery because of their well-known activity in pharmaceutical and medicinal fields [1–4]
Nitrogen-containing heterocyclic analogues have received great interest in drug discovery because of their well-known activity in pharmaceutical and medicinal fields [1–4].Benzimidazole derivatives represent an important heterocyclic class of active therapeutic agents because of their wide spectrum of biological and pharmaceutical applications including antibacterial, antifungal, antiviral, anticancer, antidiabetic, anticonvulsant, and anti-HIV agents [5,6]
The results justified that the compounds 6a,b firmly docked to the active site pockets of the target enzyme of DNA gyrase subunit B, which functionally participates in DNA
Summary
Nitrogen-containing heterocyclic analogues have received great interest in drug discovery because of their well-known activity in pharmaceutical and medicinal fields [1–4]. 1,2,3-triazoles have attracted a great deal of interest from medicinal chemists in the design and development of potential drug candidates due to their high pharmacological properties such as antimicrobial, antitubercular, CNS depressant, and antihypertensive activities [7–12]. In contribution light of the potential therapeutic propertiestoofidentify these heterocyclic compounds and agents, novel set of of hybrid derivatives benzimidazole and class triazole moieties with thea contribution our research workbearing [18,22–31]. Their antimicrobial activities were benzimidazole performed in vitro. The and to understand binding mode of performed the interactions screened compounds against molecular dockingthe study was both of to the support the antibacterial activity the site of thethe target enzyme. Drug-likeness of the prepared compounds were calculated to identify their bioavailability and toxicity
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