Design, Synthesis and Structure-Activity Relationship Studies of Nicotinamide Derivatives as Potent Antifungal Agents by Disrupting Cell Wall

Fungal infections pose a serious challenge to human health due to the limited paucity of antifungal treatments. Starting as a hit compound screened from our compound library, a series of nicotinamide derivatives have been successfully synthesized via a facile one-step coupling reaction of aromatic c...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2023-01, Vol.28 (3), p.1135
Main Authors: Ni, Tingjunhong, Xie, Fei, Li, Liping, Hao, Yumeng, Chi, Xiaochen, Yan, Lan, Zhang, Dazhi, Jiang, Yuanying, Lv, Quanzhen
Format: Article
Language:English
Subjects:
antifungal
Antifungal activity
Antifungal agents
Antifungal Agents - pharmacology
Benzoic acid
Biofilms
Candida albicans
Carboxylic acids
Cell walls
Cytotoxicity
Fluconazole
Fluconazole - pharmacology
Fungal infections
Fungi
Fungicides
Health aspects
hit-to-lead
Humans
Investigations
Lead compounds
Microbial Sensitivity Tests
Minimum inhibitory concentration
Niacinamide
Niacinamide - pharmacology
Nicotinamide
Structure-Activity Relationship
Structure-activity relationships
synthesis
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Summary:Fungal infections pose a serious challenge to human health due to the limited paucity of antifungal treatments. Starting as a hit compound screened from our compound library, a series of nicotinamide derivatives have been successfully synthesized via a facile one-step coupling reaction of aromatic carboxylic acid and amine. The synthesized compounds were evaluated for their antifungal activity against SC5314. Among the 37 nicotinamide derivatives screened, compound was found to be the most active against SC5314, with an MIC value of 0.25 μg/mL and without significant cytotoxicity. The rudimentary structure-activity relationships study revealed that the position of the amino and isopropyl groups of was critical for its antifungal activity. In particular, compound showed potent activity against six fluconazole-resistant strains with MIC values ranging from 0.125-1 μg/mL and showed moderate activity against the other seven species of , three strains of and three strains of . Furthermore, compound showed fungicidal, anti-hyphal, and anti-biofilm activities , which were related to its ability to disrupt the cell wall of . Taken together, is a promising compound that is fungal-specific by targeting the cell wall and could be used as a lead compound for further investigation.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28031135