The Search for New Antibacterial Agents among 1,2,3-Triazole Functionalized Ciprofloxacin and Norfloxacin Hybrids: Synthesis, Docking Studies, and Biological Activity Evaluation

Abstract

Among all modern antibiotics, fluoroquinolones are well known for their broad spectrums of activity and efficiency toward microorganisms and viruses. However, antibiotic resistance is still a problem, which has encouraged medicinal chemists to modify the initial structures in order to combat resistant strains. Our current work is aimed at synthesizing novel hybrid derivatives of ciprofloxacin and norfloxacin and applying docking studies and biological activity evaluations in order to find active promising molecules. We succeeded in the development of a synthetic method towards 1,2,3-triazole-substituted ciprofloxacin and norfloxacin derivatives. The structure and purity of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, UV-, IR- spectroscopy. Docking studies, together with in vitro research against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Pseudomonas aeruginosa ATCC 27853, Candida albicans NCTC 885-653 revealed compounds in which activity exceeded the initial molecules.

Synthesis and biological evaluation of ciprofloxacin – 1,2,3-triazole hybrids as antitumor, antibacterial, and antioxidant agents

“…Fluoroquinolones [ 36 ] (e.g., Ciprofloxacin) are a large group of broad-spectrum bactericide antibiotics that bind and inhibit topoisomerase II (DNA gyrase) in Gram-negative bacteria and topoisomerase IV in the Gram-positive ones, which are vital for the bacterial survival. However, the number of fluoroquinolones-resistant [ 37 ] bacteria has rapidly increased which prompts scientists to conjugate these antibiotics with pharmacophoric active residues aiming to enhance their potency in overwhelming and treating pathogenic infections.…”

Hybrid Azine Derivatives: A Useful Approach for Antimicrobial Therapy

“…Hryhoriv et al [ 21 , 22 ] synthesized two new classes of hybrid derivatives analogous to fluoroquinolones, namely piperidino-quinoline 61a , b and 1,2,3-triazolo-piperidino- quinoline 62a – k , and studied their antimicrobial activities. The first class of hybrids was obtainedviaan N -alkylation reaction of piperidino-quinoline 60a , b, when the N -substituted-piperidino-quinoline hybrids 61a , b are obtained.…”

Synthesis, analysis of molecular and crystal structures, estimation of intermolecular interactions and biological properties of 1-benzyl-6-fluoro-3-[5-(4-methylcyclohexyl)-1,2,4-oxadiazol-3-yl]-7-(piperidin-1-yl)quinolin-4-one

“…Thus, hybrids of fluoroquinolones with derivatives of phenylthiazole, quinazoline, thiazolidine, thiadiazole, pyrimidine, dithienylethene, and 1,2,4-triazole are widely described in the literature (Suaifan & Mohammed, 2019;Jia & Zhao, 2021). Our scientific team has been fruitfully working in this direction (Bylov et al, 1999;Silin et al, 2004;Savchenko et al, 2007;Hryhoriv et al, 2022;Vaksler et al, 2022). At the same time, a thorough analysis of literature sources demonstrates that modification of the 3-position of fluoroquinolones is promising and insufficiently researched (Oniga et al, 2018).…”