An Insight into the Repurposing of Phytoconstituents obtained from Delhi’s Aravalli Biodiversity Park as Antifungal Agents

Title:An Insight into the Repurposing of Phytoconstituents obtained from Delhi’s Aravalli Biodiversity Park as Antifungal Agents

Volume: 24

Author(s): Amanpreet Kaur, Kalicharan Sharma, Neetika Sharma and Geeta Aggarwal*

Affiliation:

• Delhi Pharmaceutical Sciences and Research University, M.B.Road, Sector III, Pushp Vihar, New Delhi, 110017, India

Keywords: phytochemical, antifungal, Sterol 14-?-demethylase, HSP-90, docking scorphytochemical, docking score

Abstract: The global prevalence of fungal infections is alarming in both the pre- and postCOVID period. Due to a limited number of antifungal drugs, there are hurdles in treatment strategies for fungal infections due to toxic potential, drug interactions, and the development of fungal resistance. All the antifungal targets (existing and newer) and pipeline molecules showing promise against these targets are reviewed. The objective was to predict or repurpose phyto-based antifungal compounds based on a dual target inhibition approach (Sterol-14-αdemethylase and HSP-90) using a case study. In pursuit of repurposing the phytochemicals as antifungal agents, a team of researchers visited Aravalli Biodiversity Park (ABP), Delhi, India, to collect information on available medicinal plants. From 45 plants, a total of 1149 ligands were collected, and virtual screening was performed using Schrodinger Suite 2016 software to get 83 hits against both the target proteins: Sterol-14-α-demethylase and HSP-90. After analysis of docking results, ligands were selected based on their interaction against both the target proteins and comparison with respective standard ligands (fluconazole and ganetespib). We have selected Isocarthamidin, Quercetin and Boeravinone B based on their docking score and binding interaction against the HSP-90 (Docking Score -9.65, -9.22 and -9.21, respectively) and 14-α-demethylase (Docking Score -9.19, -10.76 and -9.74 respectively). The docking protocol was validated and MM/GBSA studies depicted better stability of selected three ligands (Isocarthamidin, Quercetin, Boeravinone B) complex as compared to standard complex. Further, MD simulation studies were performed using the Desmond (67) software package version 2018-4. All the findings are presented as a case study for the prediction of dual targets for the repurposing of certain phytochemicals as antifungal agents.

Cite this article as:

Kaur Amanpreet, Sharma Kalicharan, Sharma Neetika and Aggarwal Geeta*, An Insight into the Repurposing of Phytoconstituents obtained from Delhi’s Aravalli Biodiversity Park as Antifungal Agents, Infectious Disorders - Drug Targets 2024; 24 () : e020224226666 . https://dx.doi.org/10.2174/0118715265282411240119061441