In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5
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.
KeywordsACE inhibitors Clerodendrum colebrookianum Walp. Molecular docking Molecular dynamics simulation PDE5 inhibitors and ROCK inhibitors
Root mean square deviations
Root mean square fluctuations
Rho-associated coiled-coil protein kinase
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).
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflicts of interest in the present work.
- 1.Olayiwola A, Vernon H, Hugh S (1991) Conservation of medicinal plants. Cambridge University Press, CambridgeGoogle Scholar
- 3.Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, Temml V, Wang L, Schwaiger S, Heiss EH, Rollinger JM, Schuster D, Breuss JM, Bochkov V, Mihovilovic MD, Kopp B, Bauer R, Dirsch VM, Stuppner H (2015) Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv 33(8):1582–1614CrossRefGoogle Scholar
- 5.Shrivastava N, Patel T (2007) Clerodendrum and healthcare: an overview—Part II phytochemistry and biotechnology. Med Aromat Plant Sci Biotechnol 1:209–223Google Scholar
- 6.Shrivastava N, Patel T (2007) Clerodendrum and healthcare: an overview Med Aromat Plant Sci. Biotechnol 1:142Google Scholar
- 17.Janmoni K, Sureshkumar SS, Mohamed LK (2012) Clerodendrum colebrookianum Walp.: a potential folk medicinal plant of North East India. Asian J Pharm Biol Res 2(4):256–261Google Scholar
- 22.Chinta G, Ramya Chandar Charles M, Klopcic I, Sollner Dolenc M, Periyasamy L, Selvaraj Coumar M (2015) In silico and in vitro investigation of the Piperine’s male contraceptive effect: docking and molecular dynamics simulation studies in androgen-binding protein and androgen receptor. Plant Med 81(10):804–812CrossRefGoogle Scholar
- 24.Fancui M (2013) Molecular dynamics simulation of VEGFR2 with sorafenib and other urea-substituted aryloxy compounds. J Theor Chem 2013:7Google Scholar
- 25.Schrödinger LLC (2011) Maestro, version 9.2. Schrödinger LLCGoogle Scholar
- 28.Akama T, Dong C, Virtucio C, Sullivan D, Zhou Y, Zhang YK, Rock F, Freund Y, Liu L, Bu W, Wu A, Fan XQ, Jarnagin K (2013) Linking phenotype to kinase: identification of a novel benzoxaborole hinge-binding motif for kinase inhibition and development of high-potency rho kinase inhibitors. J Pharmacol Exp Ther 347(3):615–625CrossRefGoogle Scholar
- 31.Schrödinger LLC (2011) Prime, version 9.2. Schrödinger LLCGoogle Scholar
- 32.Schrödinger LLC (2011) Glide, version 9.2. Schrödinger LLCGoogle Scholar
- 47.Mishra RK, Alokam R, Singhal SM, Srivathsav G, Sriram D, Kaushik-Basu N, Manvar D, Yogeeswari P (2014) Design of novel rho kinase inhibitors using energy based pharmacophore modeling, shape-based screening, in silico virtual screening, and biological evaluation. J Chem Inf Model 54(10):2876–2886CrossRefGoogle Scholar
- 50.Chen H, Li S, Hu Y, Chen G, Jiang Q, Tong R, Zang Z, Cai L (2016) An integrated in silico method to discover novel Rock1 inhibitors: multi- complex-based pharmacophore, molecular dynamics simulation and hybrid protocol virtual screening. Comb Chem High Throughput Screen 19(1):36–50CrossRefGoogle Scholar