Synthesis of Hybridized Fluoroquinolones and Evaluation of Their Biological Properties

Introduction

The problem of resistance to antibiotics is still persistent and requires special attention. While overuse and misuse of these medicines has been in progress for many years, numerous resistant strains have appeared. Even novel active molecules are not always able to cure the infections caused by them. Still, it is possible to design new potential antibiotics based on the known pharmacophores. Our investigation is aimed at synthesis and studies of antibacterial properties of hybridized fluoroquinolones (FQ).

Experimental part

The first stage of our investigation was related to docking studies, which revealed the promising molecules among C-7 and C-3 FQ derivatives. The initial starting molecules were ciprofloxacin and norfloxacin and their C-7 position was modified with 1,2,3-triazole moiety. A convenient synthetic procedure was developed.

Then, we studied modifications of C-3 position with arylsulfonyl moiety with hybridization of C-7 and N-1. Through these stages, methods of organic synthesis were used. The structures of the obtained compounds were determined using ¹H NMR, ¹³C NMR, LC/MS spectroscopy and X-Ray diffraction studies.

Results and discussions

Modification of starting compounds with 1,2,3-triazole moiety led to novel molecules with moderate antimicrobial and antifungal activities. As for C-3 substituted arylsulfonyl derivatives, they appeared to be less soluble and, therefore, their activity was a bit smaller than for the first group. For now, these investigations are still in progress.