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Infectious Disorders - Drug Targets

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ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

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Research Article

Molecular Modeling Studies of Halogenated Imidazoles against 14α- Demethylase from Candida Albicans for Treating Fungal Infections

Author(s): Nidhi Rani*, Praveen Kumar and Randhir Singh

Volume 20, Issue 2, 2020

Page: [208 - 222] Pages: 15

DOI: 10.2174/1871526519666181130101054

Price: $65

Abstract

Background: Imidazole is one of the most explored and marketed azole utilized for the treatment of fungal infections. Lanosterol 14α-demethylase (Cytochrome P450DM) is the active target site for azole antifungals.

Aim and Objective: This study emphasized on evaluation of a series of halogenated imidazole analogues using molecular docking studies for anti-Candidal activity. Furthermore, the model was refined by molecular dynamic simulation.

Methods: Halogenated imidazole analogues (PS1-PS30) were obtained from literature for the study. The imidazole analogues were prepared using Chem sketch and molecular docking was performed using Molergo Virtual Docker program and ADMET study was carried out by using Accelry’s Accord for Excel programme.

Results: The docking study indicated that all the imidazole analogues (PS1-PS30) and standard drugs i.e., Ketoconazole, Miconazole and Clotrimazole possessed interaction with protein residue, heme cofactor and water molecule positioned above Heme cofactor of 14α-demethylase. Further, the ADMET study indicated that most of the halogenated imidazoles possessed good absorption, human intestinal absorption, aqueous solubility and blood brain penetration.

Conclusion: Halogenated imidazole analogues may be used as potential lead molecules as 14α- demethylase inhibitors.

Keywords: Antifungal agents, ADME, 14α-demethylase, imidazole, lipinski rule, molecular docking, molecular dynamic simulation.

Graphical Abstract

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