Triazolo [1,5‐a]pyrimidines as DNA Gyrase Inhibitiors: Synthesis, Antimicrobial, Activities, and in silico ADMET with Molecular Docking Studies

Abstract

AbstractThe study focused on developing new triazolopyrimidine derivatives as potential DNA Gyrase inhibitors and antimicrobial agents. The compounds were designed, synthesized, and evaluated for their biological activities, safety, and ADMET properties. Encouragingly, the initial results showed promising potency and acceptable ADME parameters, forming a strong basis for further drug development research. The newly synthesized compounds were verified through spectra, mass, and elemental analysis. Notably, several compounds exhibited significant activity against both Gram‐positive and Gram‐negative bacteria, with MIC values ranging from 100 μg/ml to 250 μg/ml. importantly, the compounds were found to be safe, with no reported adverse effects or toxicities. Among the tested compounds, compound 2 m stood out as an excellent DNA Gyrase inhibitor, with an IC50 value of 0.89 μM, comparable to the reference drug ciprofloxacin with an IC50 value of 0.91 μM. Molecular docking studies confirmed that the compounds′ binding mode and docking scores were similar to ciprofloxacin, validating their antibacterial activity via DNA Gyrase inhibition. The research provides valuable insights into the potential of these newly synthesized triazolopyrimidine derivatives as DNA Gyrase inhibitors and antimicrobial agents. Their promising antibacterial activity and safe profile make them potential candidates for further development as antimicrobial agents.