In-silico structural studies on anti-inflammatory activity of phytocompounds from the genus Andrographis

Abstract

Plant species from the genus Andrographis were used in Ayurveda and in other folklore medicines for treating ailments for centuries. In this study, we have hypothesized to evaluate the secondary metabolites as potent anti-inflammatory agents from the genus Andrographis. A library of secondary metabolites of the said genus was curated from the PubChem database and was subjected to energy minimization using UCSF Chimera software employing the AMBER force field. Initially, molecular docking was performed to evaluate the binding affinity of the curated library against the enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and 5-Lipoxygenase (5-LOX) using AutoDock Vina. This resulted in shortlisting of two metabolites Echioidinin 5-O-glucoside was bound and 5,2',6'-Trihydroxy-6,7,8-trimethoxy flavone 2'-O-glucoside with high binding affinity than standard drugs Ibuprofen and Zileuton. In addition, molecular dynamic simulation studies confirm that these compounds form relatively more stable complexes than standard drugs with the above-said enzymes. The free binding energy values using MMGBSA of the above said ligands with COX-1, COX-2, and 5-LOX were found to be −49.18 kcal/mol, −38.60 kcal/mol, and −54.27 kcal/mol respectively, Whereas the standards have −21.77 kcal/mol, −9.96 kcal/mol, and −10.29 kcal/mol. Moreover, the in-silico ADMET analysis confirms the druggability of the shortlisted compounds. Later, this work will act as a base for in-vitro and in-vivo experimental studies to validate the anti-inflammatory potential of the same.

Communicated by Ramaswamy H. Sarma

Keywords:

• Andrographis
• cyclooxygenases
• 5-lipoxygenase
• anti-inflammatory
• docking

Acknowledgments

The authors would like to thank the National Institute of Technology Andhra Pradesh and PKM acknowledges the National Institute of Technology Warangal for providing an institute fellowship. PKM and TC acknowledges the Centre for Development of Advanced Computing–Bioinformatics Resources and Applications Facility, Pune.

Data availability statement

The data will be made available on request.

Ethical statement

This work does not involve the use of humans or animals.

Disclosure statement

The authors declare that they have no conflicts of interest.

Authors’ contributions

The initial idea of screening the Andrographis genus for anti-inflammatory compounds was conceived by SD and MPJ. Docking studies and analysis were performed by MPJ. Further extensive molecular dynamics work was designed, carried out, and analysed by TC and PKM. The initial draft was prepared by MPJ & PKM. All four authors proofread and approved the final manuscript for submission.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector.