Network pharmacology-integrated molecular docking analysis of phytocompounds of Caesalpinia pulcherrima (peacock flower) as potential anti-metastatic agents

Abstract

Caesalpinia pulcherrima, or peacock flower, has been a subject of cancer therapeutics research, showing promising anti-cancer and anti-metastatic properties. The present research aims to investigate the anti-metastatic potential of the flower, through bioinformatics approaches. Metastasis targets numbering 471 were identified through overlap analysis following NCBI gene, Gene Card and OMIM query. Phytocompounds of the flower were retrieved from PubChem and their protein interactions predicted using Super-PRED and TargetNet. The 28 targets that overlapped with the predicted proteins were used to generate STRING >0.7. Enrichment analysis revealed that C. pulcherrima may inhibit metastasis through angiogenesis-related and leukocyte migration-related pathways. HSP90AA1, ESR1, PIK3CA, ERBB2, KDR and MMP9 were identified as potential core targets while and 6 compounds (3-[(4-Hydroxyphenyl)methylidene]-7,8-dimethoxychromen-4-one (163076213), clotrimazole (2812), Isovouacapenol A (636673), [(4aR,5R,6aS,7R,11aS,11bR)-4a-hydroxy-4,4,7,11b-tetramethyl-9-oxo-1,2,3,5,6,6a,7,11a-octahydronaphtho[2,1-f][1]benzofuran-5-yl] benzoate (163104827), Stigmast-5-en-3beta-ol (86821) and 4,2'-dihydroxy-4'-methoxychalcone (592216)) were identified as potential core compounds. Molecular docking analysis and molecular dynamics simulations investigations revealed that ERBB2, HSP90AA1 and KDR, along with the newly discovered 163076213 compound to be the most significant metastasis targets and bioactive compound, respectively. These three core targets demonstrated interactions consistent with angiogenesis and leukocyte migration pathways. Furthermore, potentially novel interactions, such as KDR-MMP9, KDR-PIK3CA, ERBB2-HSP90AA1, ERBB2-ESR1, ERBB2-PIK3CA and ERBB2-MMP9 interactions were identified and may play a role in crosslinking the aforementioned metastatic pathways. Therefore, the present study revealed the main mechanisms behind the anti-metastatic effects of C. pulcherrima, paving the path for further research on these compounds and proteins to accelerate the research of cancer therapeutics and application of C. pulcherrima.

Communicated by Ramaswamy H. Sarma

Keywords:

• Network
• docking
• phytocompound
• cancer
• Caesalpinia pulcherrima

Acknowledgements

This work was supported by the School of Biosciences, Faculty of Health and Medical Sciences, Taylor’s University, Malaysia.

Authors’ contributions

TYQ conceived the study idea. THD and AYWN completed the bioinformatics analysis and drafted the manuscript with contributions from all authors. TYQ reviewed and supervised the work. All authors contributed to the article and the final version of the manuscript was reviewed and approved by all the authors.

Data availability statement

All data generated or analyzed during this study are included in this published article

Disclosure statement

The authors declare that there is no conflict of interest.

Additional information

Funding

This research was supported by Ministry of Higher Education (MOHE) Malaysia through Fundamental Research Grant Scheme (FRGS/1/2020/SKK0/TAYLOR/02/2).