Design, Synthesis, and Antibacterial Screening of Some Novel Heteroaryl-Based Ciprofloxacin Derivatives as DNA Gyrase and Topoisomerase IV Inhibitors

• Main Authors: Lamya H. Al-Wahaibi (Author), Amer A. Amer (Author), Adel A. Marzouk (Author), Hesham A. M. Gomaa (Author), Bahaa G. M. Youssif (Author), Antar A. Abdelhamid (Author)
• Format: Book
• Published: MDPI AG, 2021-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

A novel series of ciprofloxacin hybrids comprising various heterocycle derivatives has been synthesized and structurally elucidated using ¹H NMR, ¹³C NMR, and elementary analyses. Using ciprofloxacin as a reference, compounds <b>1-21</b> were screened in vitro against Gram-positive bacterial strains such as <i>Staphylococcus aureus</i> and <i>Bacillus subtilis</i> and Gram-negative strains such as <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>. As a result, many of the compounds examined had antibacterial activity equivalent to ciprofloxacin against test bacteria. Compounds <b>2-6</b>, oxadiazole derivatives, were found to have antibacterial activity that was 88 to 120% that of ciprofloxacin against Gram-positive and Gram-negative bacteria. The findings showed that none of the compounds tested had antifungal activity against <i>Aspergillus flavus</i>, but did have poor activity against <i>Candida albicans</i>, ranging from 23% to 33% of fluconazole, with compound <b>3</b> being the most active (33% of fluconazole). The most potent compounds, <b>3</b>, <b>4</b>, <b>5</b>, and <b>6</b>, displayed an IC₅₀ of 86, 42, 92, and 180 nM against <i>E. coli</i> DNA gyrase, respectively (novobiocin, IC₅₀ = 170 nM). Compounds <b>4</b>, <b>5</b>, and <b>6</b> showed IC₅₀ values (1.47, 6.80, and 8.92 µM, respectively) against <i>E. coli</i> topo IV in comparison to novobiocin (IC₅₀ = 11 µM).

Item Description

10.3390/ph14050399
1424-8247