In-vitro Evaluation of the Antifungal Property of Cold-Pressed Coconut oil Against Drug-Resistant Candida albicans and in-Silico Bioactivity Against Candidapepsin-2

Abstract

Objective: This study focuses on Candida albicans, a significant fungal pathogen in humans, particularly affecting immunocompromised individuals and developing resistance to commonly used antifungal drugs. To address this challenge, the research assessed the in-vitro anti-candida properties of cold-pressed coconut oil. Additionally, the study conducted an in-silico evaluation of the oil's bioactive compounds against candidapepsin-2, an enzyme crucial in the virulence and pathogenesis of Candida infections. Materials and Methods: Extracted coconut oil was tested for its sterility and evaluated for its antifungal activity in-vitro using the agar well-diffusion methods with fluconazole as a positive control. Growth kinetics assay and synergism activity with fluconazole were also assessed. The coconut oil was quantitatively screened for its bioactive compounds using gas chromatography coupled to a mass spectrophotometer (GC-MS) and the resulting bioactive compounds were assessed for absorption, distribution, metabolism, excretion and toxicity (ADMET) properties using the SWISSADME tool. Compounds that met Lipinski's rule of five (ROF) were subjected to molecular docking against candidapepsin-2 using the Biovia (Discovery) docking tool. Results: The test isolates exhibited zones of inhibition ranging from 47–76 mm to the extract (100%) compared to 12–42 mm exhibited against fluconazole (400 mg) and 2–3 mm in plates containing only agar with MICs and MFCs ranging from 1.57–6.25% and 3.13 −12.5% against the extract compared to the control drug where MICs and MFCs of 6.25–12.5% and 12.5–25.0% were observed, respectively. The coconut extract exerted a concentration-dependent effect on the test isolates over time as higher extract concentrations decreased the optical density of cells to 0.001–0.06 at 72 h of incubation. Equal proportions of the extract + fluconazole exerted greater inhibitory potentials on the test isolates compared with those of low extract proportions. The synergistic-antagonistic antifungal assay showed enhanced sensitivity of the resistant isolates. Of the eleven (11) bioactive compounds quantitatively screened, only nine (9) met Lipinski's ROF and also returned favourable pharmacokinetics comparable to fluconazole. Docking scores for the bioactive compounds ranged from −2.0 to −3.0 kcal/mol. The most recurring amino acid residues following molecular docking were ILE and THR. Conclusion: The bioactive compounds showed desirable activities in-vitro, especially in synergy with fluconazole against the drug-resistant Candida species and in-silico and thus, require further studies to validate their potential use in the management of Candida-related infections.