New 1,3-diphenyl-1H-pyrazol-5-ols as anti-methicillin resistant Staphylococcus aureus agents: Synthesis, antimicrobial evaluation and in silico studies

• Published in: Heliyon 2024-07, Vol.10 (13), p.e33160, Article e33160
• Main Authors: Abdel Reheim, Mohamed A.M., Abdel Hafiz, Ibrahim S., Reffat, Hala M., Abdel Rady, Hend S., Shehadi, Ihsan A., Rashdan, Huda R.M., Hassan, Abdelfattah, Abdelmonsef, Aboubakr H.
• Format: Article
• Language: English
• Subjects: 4-Acetyl-1,3-diphenyl-1H-pyrazole-5(4H)-ole; Antibiotic resistance; Antimicrobial activities; DNA gyrase; Molecular docking; Pyrazole
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e33160

In the present work, two hybrid series of pyrazole-clubbed pyrimidine and pyrazole-clubbed thiazole compounds 3–21 from 4-acetyl-1,3-diphenyl-1H-pyrazole-5(4H)-ole 1 were synthesized as novel antimicrobial agents. Their chemical structures were thoroughly elucidated in terms of spectral analyses such as IR, 1H NMR, 13C NMR and mass spectra. The compounds were in vitro evaluated for their antimicrobial efficiency against various standard pathogen strains, gram -ive bacteria (Pseudomonas aeruginosa, Klebsiella pneumonia), gram + ive bacteria (MRSA, Bacillus subtilis), and Unicellular fungi (Candida albicans) microorganisms. The ZOI results exhibited that most of the tested molecules exhibited inhibition potency from moderate to high. Where compounds 7, 8, 12, 13 and 19 represented the highest inhibition potency against most of the tested pathogenic microbes comparing with the standard drugs. In addition, the MIC results showed that the most potent molecules 7, 8, 12, 13 and 19 showed inhibition effect against most of the tested microbes at low concentration. Moreover, the docking approach of the newly synthesized compounds against DNA gyrase enzyme was performed to go deeper into their molecular mechanism of antimicrobial efficacy. Further, computational investigations to calculate the pharmacokinetics parameters of the compounds were performed. Among them 7, 8, 12, 13 and 19 are the most potent compounds revealed the highest inhibition efficacy against most of the tested pathogenic microbes comparing with the standard drugs.