Exploring the potential of Andrographis paniculata for developing novel HDAC inhibitors: an in silico approach
Cancer; computational biology; MD simulation; molecular docking; PCA
Cancer is one of the dreaded diseases of the twentieth century, emerging the major global causes of human morbidity. Cancer research in the last 15 years has provided unprecedented information on the role of epigenetics in cancer initiation and progression. Histone deacetylases (HDACs) are recognized as important epigenetic markers in cancer, whose overexpression leads to increased metastasis and angiogenesis. In the current study, thirty-four (34) compounds from Andrographis paniculata were screened for the identification of potential candidate drugs, targeting three Class I HDACs (Histone deacetylases), namely HDAC1 (PDB id 5ICN), HDAC3 (PDB id 4A69) and HDAC8 (PDB id 5FCW) through computer-assisted drug discovery study. Results showed that some of the phytochemicals chosen for this study exhibited significant drug-like properties. In silico molecular docking study further revealed that out of 34 compounds, the flavonoid Andrographidine E had the highest binding affinities towards HDAC1 (?9.261 Kcal mol?1) and 3 (?9.554 Kcal mol?1) when compared with the control drug Givinostat (-8.789 and ?9.448 Kcal mol?1). The diterpenoid Andrographiside displayed the highest binding affinity (-9.588 Kcal mol?1) to HDAC8 compared to Givinostat (-8.947 Kcal mol?1). Statistical analysis using Principal Component Analysis tool revealed that all 34 phytocompounds could be clustered in four statistical groups. Most of them showed high or comparable inhibitory potentials towards HDAC target protein. Finally, the stability of top-ranked complexes (Andrographidine E-HDAC1 and HDAC3; Andrographiside-HDAC8) at the physiological condition was validated by Molecular Dynamic Simulation and MM-PBSA study. Communicated by Ramaswamy H. Sarma. 2023 Informa UK Limited, trading as Taylor & Francis Group.
Das, Debalina; Banerjee, Ritesh; Bandyopadhyay, Maumita; Nag, Anish
Journal of Biomolecular Structure and Dynamics;Volume;43;Issue;1;pp.359-371
Restricted Access; Hardcopy may be available in the library
https://doi.org/10.1080/07391102.2023.2281635 https://www.scopus.com/pages/publications/85176942419?origin=resultslist
Das D., Plant Molecular Cytogenetics and Plant Biotechnology Laboratory, Department of Botany, Centre of Advanced Studies, University of Calcutta, West Bengal, Kolkata, India; Banerjee R., School of Biological and Environmental Sciences, Shoolini University, Himachal Pradesh, Solan, India; Bandyopadhyay M., Plant Molecular Cytogenetics and Plant Biotechnology Laboratory, Department of Botany, Centre of Advanced Studies, University of Calcutta, West Bengal, Kolkata, India; Nag A., Department of Life Sciences, CHRIST (Deemed to be University), Bangalore Central Campus, Bangalore, India