In silico antifungal effect of the bioactive compound of Eucalyptus camadalensus using molecular docking approach

Abstract

Stigmasterol, a naturally occurring phytosterol, from Eucalyptus camadalensus has demonstrated potential pharmacological relevance as a modulator of the CYP51B enzyme, a critical component of the sterol biosynthesis pathway in pathogenic fungi. CYP51B, a lanosterol 14α-demethylase, plays a pivotal role in converting lanosterol into ergosterol, a key structural element of fungal cell membranes essential for theirintegrity and function. Targeting CYP51B with inhibitors has been an effective antifungal strategy, as seen with azole drugs like saperconazole and pramiconazole. Computational binding analysis suggests that Stigmasterol exhibits a competitive binding affinity for CYP51B, with binding energy values comparable to those of conventional azole antifungals. Molecular interaction analysis reveals that Stigmasterol forms a strong hydrogen bond with Serine 375, contributing to ligand stabilization within the CYP51B active site. Additional stabilization is provided by a carbon-hydrogen bond with Histidine 374, while hydrophobic interactions with residues such as Alanine 307, Isoleucine 373, and Leucine 503 enhance its affinity for the enzyme’s hydrophobic binding pocket. Furthermore, π-alkyl interactions with aromatic residues,including Tyrosine 122, Tyrosine 136, and Phenylalanine 504, reinforce ligand binding through favorable entropic contributions. This finding implies that Stigmasterol may serve as a promising lead compound for antifungal drug development, particularly in response to the increasingprevalence of resistance to synthetic antifungal agents.