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Title

Insights from the predicted structural analysis of carborane substituted withaferin A with Indoleamine - 2,3-dioxygenase as a potent inhibitor

 

Authors

Syed Hussain Basha*,$,1, Abhishek Thakur$,2,3 & Firoz A Samad4

 

Affiliation

1Innovative Informatica Technologies, Hyderabad, Telangana 500 049, INDIA; 2Birla Institute of Technology Mesra, Ranchi- 835215, INDIA; 3Department of Chemistry, University of Miami, Coral Gables, Florida 33124, USA; 4Center for Genetics and Inherited Diseases, Taibah University, PO Box 3001, Medina, Saudi Arabia. $Equal contributors;

 

Email

Syed Hussain Basha - Email: shb@innovativeinformatica.com;
hassainbasha53@gmail.com; Phone: +91 9177247605; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received August 9, 2016; Accepted November 5, 2016; Published November 30, 2016

 

Abstract

Indoleamine-2,3-dioxygenase (IDO) an immunoregulatory enzyme and emerging as a new therapeutic drug target for the treatment of cancer. Carboranes, an icosahedral arrangement of eleven boron atoms plus one carbon atom with unique pharmacological properties such low toxicity, isosterism with phenyl ring and stability to hydrolysis. On the other hand, carboranes are known to increase the interaction of ligand with non-polar region of the protein provides an excellent platform to explore these carboranes towards designing and development of novel, potent and target specific drug candidates with further enhanced binding affinities. Despite of their many potential applications, molecular modeling studies of carborane-substituted ligands with macromolecules have been rarely reported. Previously, we have demonstrated the promising high binding affinity of Withaferin-A (WA) for IDO. In this present study, we investigated the effect of carborane substitutions on WA compound towards developing novel analogs for target specific IDO inhibition with better potency. Interesting docked poses and molecular interactions for the carborane substituted WA ligands were elucidated. Based on our In-silico studies, carborane substituted at various position of WA has shown enhanced binding affinity towards IDO, worth of considering for further studies.

 

Keywords:

Carboranes, Withaferin-A, Indoleamine-2,3-dioxygenase, Anti-cancer, immunotherapy, molecular modeling, HOMO, LUMO, docking, molecular dynamic simulations.

 

Citation

Hussain Basha et al. Bioinformation 12(9): 374-380 (2016)

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.