Alkaloids of Adhatoda vasica Nees. as potential inhibitors of cyclooxygenases – an in-silico study

Abstract

Eicosanoid pathways play a crucial role in the progression and resolution of inflammation. NSAIDs act as anti-inflammatory agents by inhibiting both the isoforms of cyclooxygenases (COXs) whereas, COXIBs act as specific COX-2 inhibitors. Excessive usage of the same is linked with gastrointestinal bleeding and increased cardiovascular risk, respectively. The current in-silico study was aimed at evaluating the potential of major alkaloids of A. vasica (vasicine (VAS), vasicinone (VAE), and Deoxyvasicine (DOV)) as inhibitors of COXs. The results of the computed binding energy (ΔG) indicate that Celecoxib (CEL), DOV, and VAS have a higher affinity to COX-2, while VAE has a higher affinity to COX-1, and Mefenamic acid (MEF) was not selective. Among the alkaloids, VAE exhibited the best ΔG (of −8.2 kcal/mol) with COX-1, while VAS exhibited the best ΔG (of −8.2 kcal/mol) with COX-2. This was comparable to the ΔG exhibited by Mefenamic acid (-8.7 kcal/mol with both the COXs). With their potential to remain gastroprotective while having the ability to inhibit enzymes of both the prostaglandin and leukotriene pathways, the alkaloids of A. vasica could be promising leads for the design of Eicosanoid pathway modulators/inhibitors.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

Keywords:

• Vasicine
• Vasicinone
• Deoxyvasicine
• Anti-inflammatory
• COX-1
• COX-2
• Ahdatoda vasica
• Pyrroloquinazoline alkaloids

Acknowledgements

The authors dedicate this work as an offering to Bhagawan Sri Sathya Sai Baba, the founder chancellor of Sri Sathya Sai Institute of Higher Learning. The authors acknowledge DMACS and the COSMOS lab (CRIF) of Sri Sathya Sai Institute of Higher Learning, for extending the computational support to carry out GROMACS simulations; UGC-SAP-DRS, UGC-BSR, and DBT-BIF for the financial support and fellowship. Thanks to Prof John Zhang for insights on Internal Entropy. Thanks also to Dr Vishwanathan, Dr C Sai Manohar, Dr K N Naresh, V Srivarun and S Bharath Reddy for the help and support extended.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

PG performed the experiments, drafted the manuscript with the guidance provided by MD and BR.

Additional information

Funding

This work was supported by Department of Biotechnology, Ministry of Science and Technology (No: BT/BI/25/063/2012 (BIF-SSSIHL)); University Grants Commission - Basic Scientific Research (UGC-BSR) (No: F. 7-164/2007(BSR)).