COMPUTATIONAL INVESTIGATION OF GENIPOSIDIC ACID AS AN ANTICANCER AGENT USING MOLECULAR DOCKING, MOLECULAR DYNAMIC SIMULATION, DFT CALCULATION, AND OSIRIS-MOLINSPIRATION PROFILING

SAHA, SUPRIYO; JOSHI, BHUWAN CHANDRA; JUYAL, VIJAY; SAH, ARCHANA N

doi:10.22036/pcr.2022.359603.2177

COMPUTATIONAL INVESTIGATION OF GENIPOSIDIC ACID AS AN ANTICANCER AGENT USING MOLECULAR DOCKING, MOLECULAR DYNAMIC SIMULATION, DFT CALCULATION, AND OSIRIS-MOLINSPIRATION PROFILING

Document Type : Regular Article

Authors

SUPRIYO SAHA ¹

BHUWAN CHANDRA JOSHI ²

VIJAY JUYAL ²

ARCHANA N SAH ²

¹ SCHOOL OF PHARMACEUTICAL SCIENCES &amp;amp;amp; TECHNOLOGY, SARDAR BHAGWAN SINGH UNIVERSITY DEHRADUN

² Department of Pharmaceutical Sciences, Faculty of Technology, Sir J.C. Bose Technical Campus, Bhimtal, Kumaun University, Nainital-263136, Uttarakhand,

https://doi.org/10.22036/pcr.2022.359603.2177

Abstract

Geniposidic acid is an iridoid glycoside. Iridoid glycosides showed antitumor, anti-inflammatory, cardiovascular, anti-hepatotoxic, choleretic, hypoglycaemic, hypolipidemic, antispasmodic, antiviral, immunomodulatory, and purgative activities. In this study, we focused on an iridoid glycoside geniposidic acid and computationally established the molecule as an anticancer drug.By doing so, we performed molecular docking, molecular dynamic simulation, DFT calculation, and OSIRIS-MOLINSPIRATION profiling targeting various oncogenic receptors. Outcomes suggested that geniposidic acid showed good interactions with 4DRH, 4AG8 and 4HJO. As these receptors showed anticancer activity by interacting with peptidylprolyl isomerase, VEGFR2, and EGFR tyrosine kinase, it might be possible that geniposidic shows its activity in the same way. RMSD , RMSF , Rg , and SASA values of docked conformers create a positive impact on receptor interaction. DFT calculation stated that HOMO orbital of geniposidic acid mainly delocalized on total aglycone part, and in the case of LUMO orbital image showed that total electron cloud focused on C-O-C=C-COOH group of aglycone part. In-silico profiling of geniposidic acid showed that the molecule positively interacted with G-protein coupled receptor and nuclear receptors. This information collectively confirms that if we relaunch geniposidic acid in a pharmacologically established manner, then it will be a boon for mankind to treat cancer.

Graphical Abstract