Design, Synthesis, Docking Study of Pyrazolohydrazinopyrimidin‐4‐one Derivatives and Their Application as Antimicrobials

Abstract

New series of pyrazoles 4a-c and pyrazolopyrimidines 5a -f had been constructed. The newly synthesized compounds were assessed for their antimicrobial activity towards E. coli and P. aeruginosa (gram -ve bacteria), B. subtilis and S. aureus (gram + ve bacteria) and A. flavus and C. albicans (representative of fungi). The pyrazolylpyrimidine-2,4-dione derivative 5b is the most active candidate against B. subtilis (MIC = 60 μg/mL) and P. aeruginosa (MIC = 45 μg/mL). Regarding antifungal potential, compound 5f was the most effective against A. flavus (MIC = 33 μg/mL). Similarly, compound 5c displayed strong antifungal activity towards C. Albicans (MIC = 36 μg/mL) in reference to amphotericin B (MIC = 60 μg/mL). Finally, the novel compounds had been docked inside dihydropteroate synthase (DHPS) to suggest the binding mode of these compounds.

Construction and Docking Studies of Novel Pyrimido[4,5‐b]quinolines as Antimicrobial Agents

“…Many heterocyclic scaffolds have been found in the core structure of DHFR and/or DNA gyrase inhibitors as tetrazole, [42–44] triazole [45,46] . Depending on the aforesaid studies, motivated by the versatility of quinolones and pyrimidines as vital moieties in a lot of FDA approved antimicrobial drugs, and in addition to our recent researches focusing on identifying novel bioactive agents, [7,47–59] we combined quinolone moiety with pyrimidine ring in one hybrid forming novel series of pyrimidoquinolones adapting fragment based drug design technique. Moreover, many heterocycles of antimicrobial potential as triazole, pyrazole, Schiff base and/or thiazolidines were attached to the pyrimidoquinolones in a way to increase the antimicrobial activity of the novel designed compounds.…”