Work

Anti-Candida properties of 5-butyl-2-pyridine carboxylic acid, extracted from azole drug-sensitive micro-fungi Aspergillus fumigatus nHF-01

Year: 2025

Type: preprint

Abstract: Objectives This study aimed to evaluate the effects of 5-butyl-2-pyridinecarboxylic acid, a potent antimicrobial compound from Aspergillus fumigatus , on growth inhibition, biofilm formation, biofilm destabilization, and cellular integrity in four Candida species. Materials and Methods The anti- Candida activity of 5-butyl-2-pyridinecarboxylic acid was assessed using disk diffusion and microdilution assays to determine minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). Growth kinetics were monitored through growth curve and time-kill assays, while synergistic effects with standard antifungal drugs were evaluated using fractional inhibitory concentration (FIC) indices. Cellular damage was analyzed by scanning electron microscopy (SEM) and lactate dehydrogenase (LDH) release assays. Biofilm inhibition and destabilization were determined using microtiter plate assays with crystal violet staining. A molecular docking study was done to predict the potential target of action. Results The compound exhibited potent inhibitory activity, with MIC and MFC values ranging from 0.129 ± 0.013 to 0.258 ± 0.012 mg/ml. At concentrations between 0.128 and 0.258 mg/mL, it induced rapid loss of viability and complete lethality within 15 hours. SEM and LDH assays revealed significant cell wall disruption and increased permeability. Time-kill kinetics confirmed potent fungicidal activity. The compound also showed synergistic effects with clotrimazole and luliconazole against C. albicans and C. glabrata , while an additive effect was observed against C. parapsilosis . It showed antibiofilm activity as compared to usnic acid. 5-butyl-2-pyridine carboxylic acid was predicted to be a potential target of the ergosterol biosynthetic enzyme Lanosterol 14α-demethylase (LDM) (CYP51) of C. glabrata and its correlated isoform ERG11 of C. albicans . Conclusions This study highlights the promising anti- Candida potential of 5-butyl-2-pyridine carboxylic acid. By disrupting cell walls, increasing membrane permeability, exhibiting synergism with conventional antifungals, and being predicted to inhibit 14α-demethylase (CYP51), the compound represents a potential lead candidate. Further safety and mechanistic studies are needed to explore its application in antifungal drug development.

Source: Research Square

DOI: 10.21203/rs.3.rs-10593573/v1

Authors: Vivekananda Mandal, Rajsekhar Adhikary, Narendra Nath Ghosh, Sayan Poddar, VIVEKANANDA MANDAL

Institutions: University of Gour Banga, Manhattan High School, Pocatello High School, Pokhara Academy of Health Sciences, Indian Institute of Technology Roorkee

Language: English

Topic: Antifungal resistance and susceptibility

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: Department of Biotechnology, Ministry of Science and Technology, India