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In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5

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Abstract

Understanding the molecular mode of action of natural product is a key step for developing drugs from them. In this regard, this study is aimed to understand the molecular-level interactions of chemical constituents of Clerodendrum colebrookianum Walp., with anti-hypertensive drug targets using computational approaches. The plant has ethno-medicinal importance for the treatment of hypertension and reported to show activity against anti-hypertensive drug targets—Rho-associated coiled-coil protein kinase (ROCK), angiotensin-converting enzyme, and phosphodiesterase 5 (PDE5). Docking studies showed that three chemical constituents (acteoside, martinoside, and osmanthuside β6) out of 21 reported from the plant to interact with the anti-hypertensive drug targets with good glide score. In addition, they formed H-bond interactions with the key residues Met156/Met157 of ROCK I/ROCK II and Gln817 of PDE5. Further, molecular dynamics (MD) simulation of protein–ligand complexes suggest that H-bond interactions between acteoside/osmanthuside β6 and Met156/Met157 (ROCK I/ROCK II), acteoside and Gln817 (PDE5) were stable. The present investigation suggests that the anti-hypertensive activity of the plant is due to the interaction of acteoside and osmanthuside β6 with ROCK and PDE5 drug targets. The identified molecular mode of binding of the plant constituents could help to design new drugs to treat hypertension.

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Abbreviations

ACE:

Angiotensin-converting enzyme

MD:

Molecular dynamics

PDE5:

Phosphodiesterase 5

PE:

Potential energy

RMSD:

Root mean square deviations

RMSF:

Root mean square fluctuations

ROCK:

Rho-associated coiled-coil protein kinase

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Acknowledgements

HA thanks University Grants Commission (UGC), Government of India, for Rajiv Gandhi National Fellowship (F1-17.1/2012-13/RGNF-2012-13-SC-RAJ-29230) to pursue his PhD degree, and MSC thanks the Department of Biotechnology (DBT), Government of India for providing financial assistance (DBT’s Twining programme for North East-BT/246/NE/TBP/2011/77).

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Authors and Affiliations

  1. Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry, 605014, India

    Hemant Arya, Safiulla Basha Syed, Dinakar R. Ampasala & Mohane Selvaraj Coumar

  2. DBT-Interdisciplinary Program in Life Sciences, Pondicherry University, Kalapet, Puducherry, 605014, India

    Safiulla Basha Syed

  3. Department of Forestry, North Eastern Regional Institute of Science and Technology (Deemed University), Nirjuli, 791109, India

    Sorokhaibam Sureshkumar Singh

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  1. Hemant Arya
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Arya, H., Syed, S.B., Singh, S.S. et al. In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5. Interdiscip Sci Comput Life Sci 10, 792–804 (2018). https://doi.org/10.1007/s12539-017-0243-6

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