Design, Synthesis, and In Silico Studies of New Norfloxacin Analogues with Broad Spectrum Antibacterial Activity via Topoisomerase II Inhibition
Abstract
Background: Novel norfloxacin derivatives were synthesized, characterized, and screened for their antibacterial activity against Gram-positive strain S. aureus ATCC 6538 and Gram-negative strains; E. coli ATCC 25923, K. pneumoniae ATCC 10031, and P. aeruginosa ATCC 27853 using the agar cup diffusion method. Results: The results revealed that compounds 6–17 exhibited more potent activity towards S. aureus ATCC 6538 with MIC values of 0.21–3.61 µM than norfloxacin with a MIC of 7.83 µM. The most potent compound, 6, showed 37-fold more potency than norfloxacin. More importantly, compound 7 exhibited more potent activity against MRSA than norfloxacin, with MIC values of 0.80 and 1.96 µM, respectively. Meanwhile, compounds 15 and 16 have potent activity towards the Gram-negative strains with MIC values of 0.20–0.79 µM compared with norfloxacin with a MIC of 0.24 µM. Moreover, the potent compounds showed higher activity towards topoisomerase II enzymes, especially against topoisomerase IV, which confirms the docking study with the S. aureus gyrase enzyme active binding site (PDB ID: 2XCT). In addition, cytotoxicity assays of the most potent compounds showed that compounds 6, 7, 15, and 16 have negligible risks of toxic effects when evaluated against the normal cell line WI 38. Conclusions: The docking study of the most potent compounds 6, 7, 15, and 16 on the gyrase enzyme active site (PDB: 2XCT) aligns their antibacterial activity and topoisomerase inhibition. The physicochemical…
Read the paper
Related studies
- Association of lower urinary tract symptoms and OAB severity with quality of life and mental health in China, Taiwan and South Korea: results from a cross-sectional, population-based study
- Ten-Day Quadruple Therapy Comprising Low-Dose Rabeprazole, Bismuth, Amoxicillin, and Tetracycline Is an Effective and Safe First-Line Treatment for Helicobacter pylori Infection in a Population with High Antibiotic Resistance: a Prospective, Multicenter, Randomized, Parallel-Controlled Clinical Trial in China
- The Role of the NLR and PLR in Urinary Tract Infection
- Threat of Antimicrobial Resistance among Pilgrims with Infectious Diseases during Hajj: Lessons Learnt from COVID-19 Pandemic
- Leclercia adecarboxylata urinary tract infection in a patient with bladder cancer and recurrent hematuria
- A Case Series of Staphylococcus lugdunensis Infection in Cancer Patients at an Academic Cancer Institute in the United States
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.