Targeting fungal biofilms: design, synthesis, biological and in silico studies of novel N-(5-undecyl-1,3,4-oxadiazol-2-yl)benzamide derivatives against Candida albicans

Kumar, A. C. and Madalambika and Bharathkumar, P. M. and Patil, Priyanka, R and Rangaswamy (2025) Targeting fungal biofilms: design, synthesis, biological and in silico studies of novel N-(5-undecyl-1,3,4-oxadiazol-2-yl)benzamide derivatives against Candida albicans. Bioorganic & Medicinal Chemistry, 131. ISSN 09680896

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Abstract

The inhibition of fungal biofilm formation has garnered significant attention as a promising therapeutic strategy against fungal infections. In this study, a series of N-(5-undecyl-1,3,4-oxadiazol-2-yl)benzamide derivatives 5(a–o) were synthesized as novel biofilm inhibitors targeting Candida albicans, utilizing the well-known biological activities linked with the oxadiazole nucleus. The in vitro antifungal activity of all derivatives was evaluated using the broth microdilution method, with fluconazole serving as the reference drug. Notably, compound 5e exhibited potent activity, with a minimum inhibitory concentration (MIC) of 7 μg/mL and a minimum fungicidal concentration (MFC) of 32 μg/mL, outperforming the standard drug (MIC: 8 μg/mL; MFC: 64 μg/mL). Biofilm and hyphal filament inhibition assays further revealed that compound5eachieved 86.29 %inhibition of biofilm formation and72.30 %inhibition of fungal filamentation. Additionally, RT-PCR analysis demonstrated that treatment with compound5esignificantly downregulated the expression of key biofilm genes, including ALS1, ALS3, and HWP1. Scanning electron microscopy (SEM) of C. albicans treated with5e confirmed substantial inhibition of biofilm formation compared to both untreated controls and the fluconazole-treated group. Screening of compound5efor blood compatibility by hemolytic assay revealed4.83 %cell lysis at 1125 μg/mL, and cytotoxicity assay on human HEK293 cell line demonstrated that compound 5e was non-toxic to normal cells at the tested concentrations. Further more, molecular docking studies to investigate the potential binding interactions of the lead compound, along with ADMET analysis, were performed to assess pharmacokinetic and bioavailability profiles. The enhanced bioactivity of compound 5eis associated with the presence of an ortho-substituted hydroxy group, a 1,3,4-oxadiazole core, and a long hydrophobic alkyl chain, which collectively improve target binding, membrane interaction, and antifungal effectiveness. These findings suggest that compound5eis a promising candidate for the development of next-generation antifungal agents to combat drug-resistant Candida albicans infections. © 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Item Type:	Article
Uncontrolled Keywords:	5-Undecyl-1,3,4-Oxadiazole-2-benzamideCandida albicansBiofilm inhibitionFilament inhibitionHemolysisCytotoxicitySAR studiesMolecular dockingADMET
Subjects:	C Chemical Science > Chemistry
Divisions:	Department of > Chemistry
Depositing User:	Vasantha library uom
Date Deposited:	21 Nov 2025 09:51
Last Modified:	21 Nov 2025 09:51
URI:	http://eprints.uni-mysore.ac.in/id/eprint/17973

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