SYNTHESIS AND MOLECULAR DOCKING STUDIES OF ETHYL 1-BENZENESULFONYL -2-[(E)-2-(2 METHYLPHENYL) ETHENYL] INDOLE -3-CARBOXYLATE WITH HUMAN RENIN COMPLEXED WITH INHIBITOR
Abstract
Various proteins play important roles in hypertension and a number of drugs have been tested for their efficacy in modulating hypertension. Renin is an aspartyl protease involved in the production of angiotensin II, a potent vasoconstrictor. Renin inhibitors can prevent blood vessel constriction and therefore could be useful for the treatment of hypertension. With this rationale, some new indole compound are synthesized and evaluated for their antihypertensive activity. Docking studies using Molegro Virtual Docker (MVD) on the human Renin complexed with inhibitor (PDB ID : 2IKO) show their role in the antihypertensive activity of the molecule and explain the higher potency of compound based on ReRanking score and binding poses of the molecule.
Keywords: Indole, Human Renin complexed with inhibitor, Molegro Virtual Docker, Antihypertensive, Single XRD.
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References
Zoccali C, Mallamaci F, Tripepi G (2002) Hypertension as a cardiovascular risk factor in
end-stage renal failure. Curr Hypertens Rep 4: 381-386.
Chow WH, Gridley G, Jr Fraumeni JF, Järvholm B (2000) Obesity, hypertension, and the risk
of kidney cancer in men. N Engl J Med 343: 1305- 1311.
Johnson RJ, Segal MS, Sautin Y, Nakagawa T, Feig DI, et al. (2007) Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease.Am J Clin Nutr 86: 899-906.
Stokes J III, Kannel WB, Wolf PA, Cupples LA, D'Agostino RB (1987) The relative importance of selected risk factors for various manifestations of cardiovascular disease among men and women from 35 to 64 years old: 3 years of follow-up in the Framingham Study. Circulation 75: 65-73
Charles., High Blood Pressure Ages The Brain. The Lancet (05 November , 2012).
Abele, E.; Abele, R.; Dzenitis, O.; Lukevics, E. Chem Heterocyc Compd 2003, 39, 3.
Radwan, M. A. A.; Ragab, E. A.; Sabry, N. M.; Shenawy,S. M. E. Bioorg Med Chem 1997, 15, 3832.
Kalaskar, G. P.; Girisha, M.; Purohit, M. G.; Thippeswamy,B. S.; Patil, B. M. Indian J Heterocycl Chem 2007, 16, 325.
Rani, P.; Srivastava, V. K.; Kumar, A. Eur J Med Chem 2004, 39, 449.
Amir, M.; Dhar, N.; Tiwari, S. K. Indian J Chem 1997, 36B, 96.
Skii, N. M. P.; Magedov, I. V.; Drozd, V. N. Chem Heterocycl Compd 1997, 33, 1475.
Panwar, H.; Verma, R. S.; Srivastava, V. K.; Kumar, A. Indian J Chem 2006, 45B, 2099.
Hiari, Y. M. A.; Qaisi, A. M.; Abadelah, M. M.; Voelter,W. Monatshefte Fur Chemie 2006, 137, 243.
Sharma, K.; Jain, R.; Joshi, K. C. Indian J Heterocycl Chem 1992, 1, 189.
Hong, B. C.; Jiang, Y.; Chang, Y.; Lee, S. J Chin Chem Soc 2006, 53, 647.
Queiroz, M. R. P.; Abreu, A. S.; Carvalho, M. S. D.; Ferreira, P. M. T.; Nazareth, N.; Nascimento, M. S. Bioorg Med Chem 2008, 16, 5584.
Zheng, M.; Zheng, M.; Ye, D.; Deng, Y.; Qiu, S.; Luo, X.; Chen, K.; Liu, H.; Jiang, H. Bioorg Med Chem Lett 2007, 17, 2414.
Merino, I.; Monge, A.; Font, M.; Irujo, J. J. M.; Alberdi, E.; Santiago, E.; Prieto, I.; Lasarte,
J. J.; Sarobe, P.; Borra´s, F. I Farmaco 1999, 54, 255.
Enein, H. Y. A.; Kruk, I.; Lichszteld, K.; Michalska, T.; Kiadna, A.; Marczynski, S.; Olgen,
S. Luminescence 2004, 19, 1.
Talaz, O.; Gulcin, I.; Goksu, S.; Saracoglu, N. Bioorg Med Chem 2009, 17, 6583.
Karali, N.; Gursoy, A.; Kandemirli, F.; Shvets, N.; Kaynak, F. B.; Ozbey, S.; Kovalishyn, V.; Dimoglo, A. Bioorg Med Chem 2007, 15, 5888.
Himaja M, Vandana K, Ranjitha A, Rahman MV, Karigar A A, Synthesis, docking studies
and antioxidant activity of 1,3- Benzodioxole -5- carboxyl amino acids and dipeptides, international Research Journal of Pharmacy, 2011; 2(6): 57-61.
C. Ramathilagam; V. Saravanan; A. K. Mohanakrishnan; G. Chakkaravarthi,; P. R. Umarani and V. Manivannan. Acta Cryst. (2011). E67, o448.
http://www.rcsb.org/ pdb.
http://www.modelling.leeds.ac.uk/pocketfinder
http://www.molegro.com/mvd-product.php
Thomsen R & Christensen MH. J Med Chem. 2006 49: 3315 [PMID: 16722650]
Hamsa NS , Vandana PN , Vivek Chandramohan , Seema JP. Pharmacophore elucidation and docking studies on anti-inflammatory compounds of medicinal plants for ulcerative colitis. Asian journal of pharmaceutical and clinical research 2013; 6(3): 56-61.
Thangathirupathi A, Naushad Ali, Natarajan P, Ramesh Kumar. Molecular Docking Studies of Andrographolide with Xanthine Oxidase. Asian journal of pharmaceutical and clinical research 2013; 6(2): 300-302.
Chan WP, Fung ML, Nobiling R, Leung PS. Activation of local rennin- angiotensin system
by chronic hypoxia. Molec Cell Endocrinol. 2000;160:107-14
Ogbru O. "ACE Inhibitors (Angiotensin Converting Enzyme Inhibitors)". Medicine Net.com. MedicineNet, Inc.
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