Design, synthesis, and biological evaluation of pyrazole-ciprofloxacin hybrids as antibacterial and antibiofilm agents against Staphylococcus aureus .

Autor: Ommi O; Work carried out at Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER) Balanagar Hyderabad 500037 Telangana India., Dhopat PS; Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER) Balanagar Hyderabad 500037 Telangana India yvmadhavi.niperhyd@gov.in., Sau S; Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER) Balanagar Hyderabad 500037 Telangana India nitin.kalia@niperhyd.ac.in., Estharla MR; Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER) Balanagar Hyderabad 500037 Telangana India nitin.kalia@niperhyd.ac.in., Nanduri S; Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER) Balanagar Hyderabad 500037 Telangana India yvmadhavi.niperhyd@gov.in., Kalia NP; Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER) Balanagar Hyderabad 500037 Telangana India nitin.kalia@niperhyd.ac.in., Yaddanapudi VM; Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER) Balanagar Hyderabad 500037 Telangana India yvmadhavi.niperhyd@gov.in.
Jazyk: angličtina
Zdroj: RSC medicinal chemistry [RSC Med Chem] 2024 Oct 22. Date of Electronic Publication: 2024 Oct 22.
DOI: 10.1039/d4md00623b
Abstrakt: In our continued efforts to tackle antibiotic resistance, a new series of pyrazole-ciprofloxacin hybrids were designed, synthesized, and evaluated for their antibacterial activity against Staphylococcus aureus ( S. aureus ), Pseudomonas aeruginosa ( P. aeruginosa ), and Mycobacterium tuberculosis ( Mtb ). Most of the compounds exhibited good to excellent activities against S. aureus , and six compounds (7a, 7b, 7d, 7g, 7k, and 7p) exhibited higher or comparable activity (MIC = 0.125-0.5 μg mL -1 ) to ciprofloxacin (0.125 μg mL -1 ). Further, these selected compounds were non-toxic (CC 50 ≥ 1000 μg mL -1 ) when evaluated for cell viability test against the Hep-G2 cell line. Three compounds (7a, 7d, and 7g) demonstrated excellent activity against ciprofloxacin-resistant S. aureus with MIC values ranging from 0.125-0.5 μg mL -1 and good antibiofilm activity. Among them, 7g displayed remarkable antibiofilm activity with an MBIC 50 value of 0.02 μg mL -1 , which is 50 times lower than ciprofloxacin (MBIC 50 = 1.06 μg mL -1 ). A time-kill kinetics study indicated that 7g showed both concentration and time-dependent bactericidal properties. In addition, 7g effectively inhibited DNA-gyrase supercoiling activity at 1 μg mL -1 (8× MIC). Two compounds 7b and 7d exhibited the highest activity against Mtb with a MIC of 0.5 μg mL -1 , while 7c showed the highest activity against P. aeruginosa with a MIC value of 2 μg mL -1 . Molecular docking studies revealed that 7g formed stable interactions at the DNA active site.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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