AUTHOR=Alasadi Gheith M. , Al-Obaidi Zaid
TITLE=Synthesis of novel acylated and esterified ciprofloxacin derivatives as efficient anticancer and antimicrobial agents
JOURNAL=Frontiers in Materials
VOLUME=10
YEAR=2023
URL=https://www.frontiersin.org/journals/materials/articles/10.3389/fmats.2023.1255955
DOI=10.3389/fmats.2023.1255955
ISSN=2296-8016
ABSTRACT=
Nowadays, various factors enhance the resistance of some microbes to antibiotics. Irrational antibiotic use is considered an example of such factors. Therefore, the synthesis and reporting of heterocyclic compounds with multiple biological properties are of considerable value. Ciprofloxacin is an antibiotic used to treat infections. New amidification and esterification derivatives of ciprofloxacin were synthesized. Their structure was identified and confirmed using both proton and carbon-13 nuclear magnetic resonance, mass spectrometry, and elemental analysis. With the employment of MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-terazoliumbromide) methods, in vitro anticancer activity was evaluated. The utilization of clinical and laboratory standards institute (CLSI) instructions was involved in the in vitro antimicrobial activity evaluation of the newly synthesized derivatives. In terms of anticancer activity, cell proliferation, viability, and IC50, as well as antimicrobial activities, IZD (Inhibition Zone Diameter), MIC (Minimum Inhibitory Concentrations), MBC (Minimum Bactericidal Concentrations), and MFC (Minimum Fungicidal Concentration) were measured and reported. The lowest cell proliferation and viability and IC50 for 2,3-dihydroxypropyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate (compound 5) were observed to be 27.12% and 7.83 μg/mL. In antimicrobial activity, the lowest MIC for 2,3-dihydroxypropyl 7-(4-benzoylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (compound 6c) was observed to be 2 μg/mL (against Proteus mirabilis) and the lowest MIC for 1-cyclopropyl-6-fluoro-7-(4-(4-(methylthio)benzoyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (compound 3d) was observed to be 32 μg/mL (against Candida albicans, Aspergillus fumigatus). The effects were compared with commercially available drugs, and it was observed that some derivatives have the same efficacy as abemaciclib, which is used to treat breast cancer. Some derivatives were more effective than Cefazolin and Tolnaftate, well-known antibiotics and antifungals, respectively. Finally, a fairly clear relationship between the structure of the derivatives and their biological effectiveness was observed.