Ligand Based Virtual Screening to Identify Potential Anti Cancer Ligands Similar to Withaferin A Targeting Indoleamine 2,3-Dioxygenase

S. V. G. Reddy¹*, K. Thammi Reddy² and V. Valli Kumari³

¹Department of CSE, GIT, GITAM University, Visakhapatnam, India. ²Department of CSE, GIT, GITAM University, Visakhapatnam, India. ³Department of CS and SE, College of Engineering, Andhra University, Visakhapatnam, India.

ABSTRACT: For the treatment of cancer, Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic drug target characterized by pathological immune suppression. On the other hand, Withaferin A (WA) – active constituent of Withania somnifera ayurvedic herb has shown to be having a wide range of targeted anti cancer properties. Previously, we have elucidated the potential of WA in attenuating the Indoleamine 2,3-dioxygenase for immunotherapeutic tumor arresting activity using computational approaches. In this present study, a Ligand based virtual screening with a threshold of >50% similarity was performed, based on the structure of Withaferin A using ZINC database, to perform a structure based virtual screening on IDO, targeting key residues involved in its functionality. 33 compounds were identified as promising IDO inhibitors which are similar to the structure of WA based on free binding energy and ADME constraints, compared to Withaferin A.

KEYWORDS: Indoleamine 2,3-dioxygenase; Withaferin A; docking; free binding energy

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