Phytochemicals as Potential Inhibitors of Lanosterol 14 Α-Demethylase (Cyp51) Enzyme: An in Silico Study on Sixty Molecules

Abstract

Lanosterol 14 α-demethylase (CYP51) is a key protein involved in ergosterol biosynthesis of Candida albicans and a crucial target for ergosterol synthesis inhibition. However, in the last two decades drug resistance is reported under clinical situations to most of the prescribed antifungal drugs like azole group of drugs. In this study, molecular docking of sixty plant molecules with Lanosterol 14 α-demethylase protein has been done. The homology modeling tool PHYRE2 was used to predict the structure of Lanosterol 14 α-demethylase. Predicted structure was used for docking studies with sixty plant molecules by using Autodock 1.5.6 cr2™. Among the sixty plant molecules, forty-seven were found to form hydrogen bond and the rest of the plant molecules did not form a hydrogen bond with Lanosterol 14 α-demethylase. Docking study of a library of sixty molecules revealed that 48 plant molecules showed an excellent and good binding affinity with predicted protein model Lanosterol 14 α-demethylase of Candida albicans. The binding residue comparison of docked molecules with that of Ketoconazole revealed, fourteen molecules have similar binding residue. These fourteen molecules may have a similar mode of action as that of Ketoconazole. These molecules should be screened and used to discover new antifungal therapeutic drugs.

Lavandula angustifolia Essential Oils as Effective Enhancers of Fluconazole Antifungal Activity against Candida albicans

“…It was found that linalool probably causes damage of the C. albicans cell wall and plasma membrane, what can be explained by its interaction with three important enzymes involved in their biosynthesis, including lanosterol 14-α-demethylase [ 41 ]. Other molecular docking studies performed for 60 plant-origin compounds revealed that 48 of them have shown binding affinity with lanosterol 14-α-demethylase [ 42 ]. Interesting is that, among them, there are some compounds which are present in lavender essential oils studied by us: caryophyllene oxide (excellent binding activity), geranyl acetate (good binding activity), borneol, carvone, and nerol (medium binding activity).…”

Profiling of Antifungal Activities and In Silico Studies of Natural Polyphenols from Some Plants

“…Among different reported antifungal mechanisms, rutin, and quercetin, found in our plant extracts, seem to inhibit fungal strains via inhibition of CYP51 enzyme, same as that of azole drugs. In a previous study, rutin was among the seven plant molecules showing excellent binding energy against CYP51 [ 39 ]. In the same study, quercetin formed five hydrogen bonds with HIS468, GLY307, THR311, LYS143, and TYR143, having binding energy −7.54 kcal/mol [ 39 ].…”

“…In a previous study, rutin was among the seven plant molecules showing excellent binding energy against CYP51 [ 39 ]. In the same study, quercetin formed five hydrogen bonds with HIS468, GLY307, THR311, LYS143, and TYR143, having binding energy −7.54 kcal/mol [ 39 ]. In our study, quercetin exhibited the binding energy of −8 kcal/mol to CYP51, which is in line with the previously mentioned finding.…”

Combined in vitro/in silico approaches, molecular dynamics simulations and safety assessment of the multifunctional properties of thymol and carvacrol: A comparative insight

“…Interestingly, lanosterol 14α-demethylase, also known as (CYP51), which is an indispensable protein, implied in ergosterol biosynthesis, was envisaged as an imperative cellular pathway that could be targeted to inhibit (C. albicans) growth. [54] In the present study, using virtual docking method, we have screened the two natural isomers carvacrol and thymol against the CYP51 of (C. albicans) (PDB ID: 5V5Z) in order to evaluate their antifungal properties as the need for novel antifungals became unquestionable. Molecular docking results depicted that both active compounds showed good affinities against the selected fungal target and their docking scores (ΔG) were predicted to be (À 6.3) kcal/mol and (À 6.2) kcal/mol, respectively (Table 7).…”