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A Series of Furan-Based Hydrazones: Design, Synthesis, and Evaluation of Antimicrobial Activity, Cytotoxicity and Genotoxicity

Author(s):

Mehlika Dilek Altıntop*, Belgin Sever, Özlem Atlı Eklioğlu, Merve Baysal, Rasime Demirel and Ahmet Özdemir   Pages 1 - 11 ( 11 )

Abstract:


Background: Hydrazones, frequently occurring motifs in many bioactive molecules, have attracted a great deal of interest as potent antimicrobial agents.

Objective: The aim of this work is to design and synthesize new hydrazone-based antimicrobial agents.

Method: 4-[2-((5-Arylfuran-2-yl)methylene)hydrazinyl]benzonitrile derivatives (1-10) were obtained via the reaction of 4-cyanophenylhydrazine hydrochloride with 5-arylfurfurals. Compounds 1-10 were evaluated for their antimicrobial effects using a broth microdilution method. Their cytotoxic effects on NIH/3T3 mouse embryonic fibroblast cell line were investigated using XTT assay. The most effective antimicrobial agents were investigated for their genotoxic effects using Ames MPF assay. In silico docking and Absorption, Distribution, Metabolism and Excretion (ADME) studies were also performed using Schrödinger’s Maestro molecular modeling package.

Results: The antifungal effects of the compounds were more significant than their antibacterial effects. Compound 5 bearing 3-nitrophenyl moiety was the most promising antifungal agent against Candida albicans, Trichoderma harzianum and Fusarium species, whereas compound 10 bearing 4-chloro-2-nitrophenyl moiety was the most effective antifungal agent on Aspergillus ochraceus. According to XTT and Ames MPF assays, these compounds were neither cytotoxic nor genotoxic at the concentrations tested. According to docking studies, these compounds showed good affinity to the active site of lanosterol 14α-demethylase (CYP51) and interacted with the key residues such as Hem601 and Cys470. Based on in silico ADME studies, the compounds were expected to have high oral bioavailability.

Conclusion: According to the in vitro and in silico studies, compounds 5 and 10 stand out as potential orally bioavailable antifungal agents for further studies.

Keywords:

Antimicrobial activity, cytotoxicity, molecular docking, genotoxicity, furan, hydrazone

Affiliation:

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Department of Biology, Faculty of Science, Eskişehir Technical University, 26000 Eskişehi, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir



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