Title:Repurposing of Fluvastatin Against Candida albicans CYP450 Lanosterol 14 α-demethylase, a Target Enzyme for Antifungal Therapy: An In silico and In vitro Study
VOLUME: 19 ISSUE: 7
Author(s):Ritika Rana, Ruchika Sharma and Anoop Kumar*
Affiliation:Department of Pharmacology, Indo-Soviet Friendship Pharmacy College (ISFCP), Moga, Punjab, Department of Biotechnology, Indo-Soviet Friendship College of Professional Studies (ISFCPS), Moga, Punjab, Department of Pharmacology, Indo-Soviet Friendship Pharmacy College (ISFCP), Moga, Punjab
Keywords:Candida albicans, homologous model, fluvastatin, docking study, in vitro study, ex vivo study.
Abstract:
Background: The incidence of fungal infections has increased significantly.
Specifically the cases of candida albicans infection are increasing day by day and their
resistance to clinically approved drugs is a major concern for humans. Various classes
of antifungal drugs are available in the market for the treatment of these infections but
unfortunately, none of them is able to treat the infection.
Objectives: Thus, in the present investigation, we have repurposed the well-known drug
(Fluvastatin) in the treatment of Candida albicans infections by using in silico, in vitro
and ex vivo techniques.
Material and Methods: Computational and in vitro techniques.
Results: Firstly, we developed and validated a simple model of CYP45014α-lanosterol
demethylase of Candida albicans by using crystal structure of Mycobacterium
tuberculosis (1EA1). Further, fluvastatin was docked with a validated model of
CYP45014α-lanosterol demethylase and revealed good binding affinity as that of
fluconazole. In vitro results (Percentage growth retardation, Fungal growth kinetics,
Biofilm test and Post antifungal test) have shown good antifungal activity of fluvastatin.
Finally, the results of MTT assay have shown non-cytotoxic effect of fluvastatin in murine
splenocytes and thymocytes.
Conclusion: However, further in vivo studies are required to confirm the complete role
of fluvastatin as an antifungal agent.