Login Register Cart 0
Review Article

Computational and Pharmacogenomic Insights on Hypertension Treatment: Rational Drug Design and Optimization Strategies

Author(s): Lakshmanan Loganathan, Krishnasamy Gopinath, Vadivel Murugan Sankaranarayanan, Ritushree Kukreti, Kannan Rajendran, Jung-Kul Lee* and Karthikeyan Muthusamy*

Volume 21, Issue 1, 2020

Page: [18 - 33] Pages: 16

DOI: 10.2174/1389450120666190808101356

Price: $65

Abstract

Background: Hypertension is a prevalent cardiovascular complication caused by genetic and nongenetic factors. Blood pressure (BP) management is difficult because most patients become resistant to monotherapy soon after treatment initiation. Although many antihypertensive drugs are available, some patients do not respond to multiple drugs. Identification of personalized antihypertensive treatments is a key for better BP management.

Objective: This review aimed to elucidate aspects of rational drug design and other methods to develop better hypertension management.

Results: Among hypertension-related signaling mechanisms, the renin-angiotensin-aldosterone system is the leading genetic target for hypertension treatment. Identifying a single drug that acts on multiple targets is an emerging strategy for hypertension treatment, and could be achieved by discovering new drug targets with less mutated and highly conserved regions. Extending pharmacogenomics research to include patients with hypertension receiving multiple antihypertensive drugs could help identify the genetic markers of hypertension. However, available evidence on the role of pharmacogenomics in hypertension is limited and primarily focused on candidate genes. Studies on hypertension pharmacogenomics aim to identify the genetic causes of response variations to antihypertensive drugs. Genetic association studies have identified single nucleotide polymorphisms affecting drug responses. To understand how genetic traits alter drug responses, computational screening of mutagenesis can be utilized to observe drug response variations at the protein level, which can help identify new inhibitors and drug targets to manage hypertension.

Conclusion: Rational drug design facilitates the discovery and design of potent inhibitors. However, further research and clinical validation are required before novel inhibitors can be clinically used as antihypertensive therapies.

Keywords: Computational mutagenesis, drug discovery, hypertension, blood pressure, pharmacogenomics, SNPs, RAAS.

« Previous Next »
Graphical Abstract

[1]
WHO. Global Health Observatory (GHO) data [homepage on the Internet]. World Heal Organ.. https://www.who.int/gho/ncd/en/ (Accessed November 04, 2018)
[2]
Benjamin EJ, Virani SS, Callaway CW, et al. American heart association council on epidemiology and prevention statistics committee and stroke statistics subcommittee. Heart disease and stroke statistics-2018 update: A report from the american heart association. Circulation 2018; 137(12): e67-e492.
[http://dx.doi.org/10.1161/CIR.0000000000000558] [PMID: 29386200]
[3]
Arwood MJ, Cavallari LH, Duarte JD. Pharmacogenomics of hypertension and heart disease. Curr Hypertens Rep 2015; 17(9): 586.
[http://dx.doi.org/10.1007/s11906-015-0586-5] [PMID: 26272307]
[4]
Williams B, Cockcroft JR, Kario K, et al. Effects of sacubitril/valsartan versus olmesartan on central hemodynamics in the elderly with systolic hypertension: The parameter study. Hypertension 2017; 69(3): 411-20.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.08556] [PMID: 28093466]
[5]
Toto RD. Treatment of hypertension in chronic kidney disease. Semin Nephrol 2005; 25(6): 435-9.
[http://dx.doi.org/10.1016/j.semnephrol.2005.05.016] [PMID: 16298269]
[6]
Tabassum N, Ahmad F. Role of natural herbs in the treatment of hypertension. Pharmacogn Rev 2011; 5(9): 30-40.
[http://dx.doi.org/10.4103/0973-7847.79097] [PMID: 22096316]
[7]
Vm M, Kak L, Pm F, Bassett K, Jm W. Blood pressure lowering efficacy of renin inhibitors for primary hypertension ( Review ) Summary of Findings for the Main Comparison Cochrane Database Syst Rev 2017. (4)
[8]
Shrout T, Rudy DW, Piascik MT. Hypertension update, JNC8 and beyond current opinion in pharmacology. Elsevier Ltd 2017; pp. 41-6.
[9]
Rose R, Balakrishnan A, Muthusamy K, Arumugam P, Shanmugam S, Gopalswamy J. Myocilin mutations among POAG patients from two populations of Tamil Nadu, South India, a comparative analysis. Mol Vis 2011; 17(December): 3243-53.
[PMID: 22194650]
[10]
Gupta R. Trends in Hypertension Epidemiology in India 2004; 73-8.
[11]
Cover Story _ The 2017 High Blood Pressure Guideline_ Risk Reduction Through Better Management - American College of Cardiology American College of Cardiology 2017.
[12]
Kario K, Tomitani N, Buranakitjaroen P, et al. HOPE Asia Network. Rationale and design for the Asia BP@Home study on home blood pressure control status in 12 Asian countries and regions. J Clin Hypertens (Greenwich) 2018; 20(1): 33-8.
[http://dx.doi.org/10.1111/jch.13145] [PMID: 29265725]
[13]
Dymond JN, Rarities C. Bird Report. 1972.Systematic List 1976. Vol. 39
[14]
Kim TJ, Lee JW, Kang HT, et al. Trends in Blood Pressure and Prevalence of Hypertension in Korean Adults Based on the 1998-2014 KNHANES. Yonsei Med J 2018; 59(3): 356-65.
[http://dx.doi.org/10.3349/ymj.2018.59.3.356] [PMID: 29611397]
[15]
Ohno Y, Sone M, Inagaki N, et al. Nagahama study JPAS study group. Prevalence of cardiovascular disease and its risk factors in primary aldosteronism: A multicenter study in japan. Hypertension 2018; 71(3): 530-7.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.10263] [PMID: 29358460]
[16]
Franklin SS. Hypertension in older people: part 2. J Clin Hypertens (Greenwich) 2006; 8(7): 521-5.
[http://dx.doi.org/10.1111/j.1524-6175.2006.05116.x] [PMID: 16849907]
[17]
Staessen JA, Byttebier G, Buntinx F, Celis H, O’Brien ET, Fagard R. Ambulatory blood pressure monitoring and treatment of hypertension investigators. Antihypertensive treatment based on conventional or ambulatory blood pressure measurement. A randomized controlled trial. JAMA 1997; 278(13): 1065-72.
[http://dx.doi.org/10.1001/jama.1997.03550130039034] [PMID: 9315764]
[18]
Baker MD, Bell LMAJ. The new england journal of medicine downloaded from Nejm.Org at GEORGE WASHINGTON UNIVERSITY on March 4, 2012. For personal use only. No other uses without permission. Copyright © 1993 Massachusetts medical society. All Rights Reserved. N Engl J Med 1993; 329(20): 1437-41.
[http://dx.doi.org/10.1056/NEJM199311113292001] [PMID: 8413453]
[19]
Lupoli S, Salvi E, Barcella M, Barlassina C. Pharmacogenomics considerations in the control of hypertension. Pharmacogenomics 2015; 16(17): 1951-64.
[http://dx.doi.org/10.2217/pgs.15.131] [PMID: 26555875]
[20]
Fox LS, Schooley WR, Nichols RL, Webb WR. Open cardiac operations in patients with abnormalities of white blood cell number or function. South Med J 1988; 81(8): 1065-6.
[http://dx.doi.org/10.1097/00007611-198808000-00033] [PMID: 2970115]
[21]
Wassertheil-Smoller S, Fann C, Allman RM, et al. The SHEP Cooperative Research Group. Relation of low body mass to death and stroke in the systolic hypertension in the elderly program. Arch Intern Med 2000; 160(4): 494-500.
[http://dx.doi.org/10.1001/archinte.160.4.494] [PMID: 10695689]
[22]
Alderman MH, Cohen HW, Sealey JE, Laragh JH. Plasma renin activity levels in hypertensive persons: their wide range and lack of suppression in diabetic and in most elderly patients. Am J Hypertens 2004; 17(1): 1-7.
[http://dx.doi.org/10.1016/j.amjhyper.2003.08.015] [PMID: 14700504]
[23]
Banic A, Benkovic V, Knezevic A. Effectiveness of hypertension therapy by using fixed combinations and monocomponent drugs - A prospective study from croatia. J Pharm Pharmacol 2018; 6: 333-9.
[24]
Mehanna M, Gong Y, McDonough CW, et al. Blood pressure response to metoprolol and chlorthalidone in European and African Americans with hypertension. J Clin Hypertens (Greenwich) 2017; 19(12): 1301-8.
[http://dx.doi.org/10.1111/jch.13094] [PMID: 28940643]
[25]
Gong Y, Wang Z, Beitelshees AL, et al. Pharmacogenomic genome-wide meta-analysis of blood pressure response to β-blockers in hypertensive african americans. Hypertension 2016; 67(3): 556-63.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.06345] [PMID: 26729753]
[26]
Baker JH. Meditation for Reducing CVD Risk. Integrative Medicine Alert 2018; pp. 57-60.
[27]
Kaufman AL, Spitz J, Jacobs M, et al. Evidence for clinical implementation of pharmacogenomics in cardiac drugs. Mayo Clin Proc 2015; 90(6): 716-29.
[http://dx.doi.org/10.1016/j.mayocp.2015.03.016] [PMID: 26046407]
[28]
Feldman RD, Hussain Y, Kuyper LM, McAlister FA, Padwal RS, Tobe SW. Intraclass differences among antihypertensive drugs. Annu Rev Pharmacol Toxicol 2015; 55(1): 333-52.
[http://dx.doi.org/10.1146/annurev-pharmtox-010814-124446] [PMID: 25251994]
[29]
Guasti L, Gaudio G, Lupi A, et al. Ambulatory blood pressure parameters after canrenone addition to existing treatment regimens with maximum tolerated dose of angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor blockers plus hydrochlorothiazide in uncontrolled hypertensive patients. Drug Des Devel Ther 2017; 11: 2293-300.
[http://dx.doi.org/10.2147/DDDT.S134826] [PMID: 28831241]
[30]
Menni C. Blood pressure pharmacogenomics: gazing into a misty crystal ball. J Hypertens 2015; 33(6): 1142-3.
[http://dx.doi.org/10.1097/HJH.0000000000000574] [PMID: 25923729]
[31]
Cooper-DeHoff RM, Johnson JA. Hypertension pharmacogenomics: in search of personalized treatment approaches. Nat Rev Nephrol 2016; 12(2): 110-22.
[http://dx.doi.org/10.1038/nrneph.2015.176] [PMID: 26592190]
[32]
Barton Laws M, Beach M C, Lee Y, et al. The pharmacogenomics research network translational pharmacogenetics program: Overcoming challenges of real- world implementation NIH public access 2013; 17(1): 148-59.
[33]
Singh KD, Jajodia A, Kaur H, Kukreti R, Karthikeyan M. Renin angiotensin system gene polymorphisms in response to antihypertensive drugs and visit-to-visit blood pressure variability in essential hypertensive patients. Curr Pharmacogenomics Person Med 2015; 12(4): 227-35.
[http://dx.doi.org/10.2174/1875692113666150420225829]
[34]
Wang J, Shi X, Ma C, et al. Visit-to-visit blood pressure variability is a risk factor for all-cause mortality and cardiovascular disease: a systematic review and meta-analysis. J Hypertens 2017; 35(1): 10-7.
[http://dx.doi.org/10.1097/HJH.0000000000001159] [PMID: 27906836]
[35]
Wu C, Shlipak MG, Stawski RS, et al. Health ABC study. Visit-to-visit blood pressure variability and mortality and cardiovascular outcomes among older adults: The health, aging, and body composition study. Am J Hypertens 2017; 30(2): 151-8.
[http://dx.doi.org/10.1093/ajh/hpw106] [PMID: 27600581]
[36]
Dumitrescu L, Ritchie MD, Denny JC, et al. Genome-wide study of resistant hypertension identified from electronic health records. PLoS One 2017; 12(2)e0171745
[http://dx.doi.org/10.1371/journal.pone.0171745] [PMID: 28222112]
[37]
Chern TH, Chiang FT. Molecular genetic study of hypertension. Acta Cardiol Sin 2004; 20(3): 129-38.
[38]
Hackenthal E, Paul M, Ganten D, Taugner R. Morphology, physiology and molecular biology of renin secretion. Physiol Rev 1990; 70(4): 1067-116.
[39]
Fyhrquist F, Saijonmaa O. Renin-angiotensin system revisited. J Intern Med 2008; 264(3): 224-36.
[http://dx.doi.org/10.1111/j.1365-2796.2008.01981.x] [PMID: 18793332]
[40]
Lee WK, Padmanabhan S, Dominiczak AF. Genetics of hypertension: from experimental models to clinical applications. J Hum Hypertens 2000; 14(10-11): 631-47.
[http://dx.doi.org/10.1038/sj.jhh.1001043] [PMID: 11095156]
[41]
Gautam N, Kaur S, Kaur S, Kumar S. Computational Study of ACE and AGT Gene of RAAS Pathway. World News Nat Sci 2018; 19(June): 65-77.
[42]
Alanazi AM, Abdelhameed AS, Bakheit AH, et al. Spectroscopic and Molecular Docking Studies of the Binding of the Angiotensin II Receptor Blockers (ARBs) Azilsartan, Eprosartan and Olmesartan to Bovine Serum Albumin. J Lumin 2018; 203: 616-28.
[http://dx.doi.org/10.1016/j.jlumin.2018.06.085]
[43]
Karthikeyan M, Rose R, Shridevi V, et al. Core promoter variants (A-20C, T-18C and G-6A) of the angiotensinogen (AGT) gene are not significantly associated with hypertension in patients of tamilnadu, India. Int J Hum Genet 2009; 9(1): 13-9.
[http://dx.doi.org/10.1080/09723757.2009.11886056]
[44]
Rae KM, Grimson S, Pringle KG. Personalised medicine: A new approach to improving health in indigenous australian populations. Public Health Genomics 2017; 20(1): 58-62.
[http://dx.doi.org/10.1159/000455005] [PMID: 28056457]
[45]
Zhang H, Jin L, Mu T, et al. Associations of CYP4A11 gene-gene and gene-smoking interactions with essential hypertension in the male eastern Chinese Han population. Clin Exp Hypertens 2017; 39(5): 448-53.
[http://dx.doi.org/10.1080/10641963.2016.1267201] [PMID: 28534704]
[46]
Sanoski CA. Aliskiren: an oral direct renin inhibitor for the treatment of hypertension. Pharmacotherapy 2009; 29(2): 193-212.
[http://dx.doi.org/10.1592/phco.29.2.193] [PMID: 19170589]
[47]
Matsubara H. Pathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases. Circ Res 1998; 83(12): 1182-91.
[http://dx.doi.org/10.1161/01.RES.83.12.1182] [PMID: 9851935]
[48]
Zisaki A, Miskovic L, Hatzimanikatis V. Antihypertensive drugs metabolism: an update to pharmacokinetic profiles and computational approaches. Curr Pharm Des 2015; 21(6): 806-22.
[http://dx.doi.org/10.2174/1381612820666141024151119] [PMID: 25341854]
[49]
Durdagi S, Erol I, Salmas RE, Aksoydan B, Kantarcioglu I. Oligomerization and Cooperativity in GPCRs from the Perspective of the Angiotensin AT1 and Dopamine D2 Receptors. Neurosci Lett 2018.
[PMID: 29684528]
[50]
Feldman RD, Gros R. Impaired vasodilator function in hypertension: the role of alterations in receptor-G protein coupling. Trends Cardiovasc Med 1998; 8(7): 297-305.
[http://dx.doi.org/10.1016/S1050-1738(98)00022-X] [PMID: 14987554]
[51]
Brinks HL, Eckhart AD. Regulation of GPCR Signaling in Hypertension. Biochim Biophys Acta 2015; 6(9): 790-5.
[PMID: 20060896]
[52]
Majzunova M, Dovinova I, Barancik M, Chan JYH. Redox signaling in pathophysiology of hypertension. J Biomed Sci 2013; 20(69): 69.
[http://dx.doi.org/10.1186/1423-0127-20-69] [PMID: 24047403]
[53]
Paravicini TM, Touyz RM. Redox signaling in hypertension. Cardiovasc Res 2006; 71(2): 247-58.
[http://dx.doi.org/10.1016/j.cardiores.2006.05.001] [PMID: 16765337]
[54]
Giorgini P, Sahebkar A, Stamerra CA, et al. Comparison of clinical outcomes between genders following antihypertensive therapy: A meta-analysis. Curr Med Chem 2017; 24(24): 2639-49.
[http://dx.doi.org/10.2174/0929867323666161213160440] [PMID: 27978800]
[55]
Divac N, Naumović R, Stojanović R, Prostran M. The role of immunosuppressive medications in the pathogenesis of hypertension and efficacy and safety of antihypertensive agents in kidney transplant recipients. Curr Med Chem 2016; 23(19): 1941-52.
[http://dx.doi.org/10.2174/0929867323666151221150052] [PMID: 26687832]
[56]
Cruz; J. N.; Oliveira, M. S.; Vogado, J. H.; Silva, S. G.; Costa, W. A.; Fernanda, WF Bezerra; Renato, A. C.; Junior, R. N.; Neto, A. M. Molecular insights on the interactions of nitrosamines from cigarette smoking with CYP2A13 using molecular docking and molecular dynamics simulation HSOA J Pulm Med. Respir Res 2018; (August): 4.
[57]
Wen H, Wang L. Reducing effect of aerobic exercise on blood pressure of essential hypertensive patients. Medicine (United States) 2017 March;; 96(11)
[http://dx.doi.org/10.1097/MD.0000000000006150]
[58]
Turnbull F, Neal B, Algert C, et al. Blood pressure lowering treatment trialists’ collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003; 362(9395): 1527-35.
[http://dx.doi.org/10.1016/S0140-6736(03)14739-3] [PMID: 14615107]
[59]
Cushman WC, Ford CE, Cutler JA, et al. ALLHAT Collaborative Research Group. Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich) 2002; 4(6): 393-404.
[http://dx.doi.org/10.1111/j.1524-6175.2002.02045.x] [PMID: 12461301]
[60]
Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 2003; 326(7404): 1427-0.
[http://dx.doi.org/10.1136/bmj.326.7404.1427] [PMID: 12829555]
[61]
Davison KK, Birch LL. Oral direct renin inhibition: Premise, promise, and potential limitations of a new class of antihypertensive drug. Am J Med 2008; 64(12): 2391-404.
[62]
Pool JL. Direct renin inhibition: focus on aliskiren. J Manag Care Pharm 2007; 13(8)(Suppl. B): 21-33.
[http://dx.doi.org/10.18553/jmcp.2007.13.s8-b.21] [PMID: 17970614]
[63]
Pich J. The efficacy of renin inhibitors in primary hypertension. Am J Nurs 2018; 118(4): 56.
[http://dx.doi.org/10.1097/01.NAJ.0000532077.64748.d2] [PMID: 29596257]
[64]
Desjarlais M, Dussault S, Dhahri W, Mathieu R, Rivard A. Direct renin inhibition with aliskiren improves ischemia-induced neovascularization: blood pressure-independent effect. Atherosclerosis 2015; 242(2): 450-60.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.08.009] [PMID: 26295797]
[65]
Hsu CN, Lee CT, Huang LT, Tain YL. Aliskiren in early postnatal life prevents hypertension and reduces asymmetric dimethylarginine in offspring exposed to maternal caloric restriction. J Renin Angiotensin Aldosterone Syst 2015; 16(3): 506-13.
[http://dx.doi.org/10.1177/1470320313514123] [PMID: 24833625]
[66]
Buczko W, Hermanowicz JM. Pharmacokinetics and pharmacodynamics of aliskiren, an oral direct renin inhibitor. Pharmacol Rep 2008; 60(5): 623-31.
[PMID: 19066408]
[67]
Jm W, Vm M, Gill R. First-line drugs for hypertension (Review). Summary of findings for the main comparison 2018.
[68]
Carter BL, Ernst ME, Cohen JD. Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. Hypertension 2004; 43(1): 4-9.
[http://dx.doi.org/10.1161/01.HYP.0000103632.19915.0E] [PMID: 14638621]
[69]
Zillich AJ, Garg J, Basu S, Bakris GL, Carter BL. Thiazide diuretics, potassium, and the development of diabetes: a quantitative review. Hypertension 2006; 48(2): 219-24.
[http://dx.doi.org/10.1161/01.HYP.0000231552.10054.aa] [PMID: 16801488]
[70]
Hoogwerf BJ, Young JB. The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not. Cleve Clin J Med 2000; 67(4): 287-93.
[http://dx.doi.org/10.3949/ccjm.67.4.287] [PMID: 10780101]
[71]
Fein A. ACE inhibitors worsen inflammatory pain. Med Hypotheses 2009; 72(6): 757.
[http://dx.doi.org/10.1016/j.mehy.2009.01.012] [PMID: 19231090]
[72]
Ram CVS. Beta-blockers in hypertension. Am J Cardiol 2010; 106(12): 1819-25.
[http://dx.doi.org/10.1016/j.amjcard.2010.08.023] [PMID: 21126627]
[73]
Quinn U. Renin genotype as a predictor of response to antihypertensive therapy : A personalized approach to management of high blood pressure R Coll Surg Irel 2017.
[74]
Rochlani Y, Khan MH, Banach M, Aronow WS. Are two drugs better than one? A review of combination therapies for hypertension. Expert Opin Pharmacother 2017; 18(4): 377-86.
[http://dx.doi.org/10.1080/14656566.2017.1288719] [PMID: 28129695]
[75]
Dhanachandra Singh Kh. Jajodia A, Kaur H, Kukreti R, Karthikeyan M. Gender specific association of RAS gene polymorphism with essential hypertension: a case-control study. BioMed Res Int 2014; •••2014538053
[http://dx.doi.org/10.1155/2014/538053] [PMID: 24860821]
[76]
Strauss MH, Hall AS. Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARB-MI paradox. Circulation 2006; 114(8): 838-54.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.594986] [PMID: 16923768]
[77]
Weir MR, Bush C, Anderson DR, Zhang J, Keefe D, Satlin A. Antihypertensive efficacy, safety, and tolerability of the oral direct renin inhibitor aliskiren in patients with hypertension: a pooled analysis. J Am Soc Hypertens 2007; 1(4): 264-77.
[http://dx.doi.org/10.1016/j.jash.2007.04.004] [PMID: 20409858]
[78]
Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy for Hypertension in the Elderly. Cochrane Database Syst Rev 2009.
[http://dx.doi.org/10.1002/14651858.CD000028.pub2]
[79]
Food and drug administration (FDA). Hypertension: developing fixed- dose combination drugs for treatment guidance for industry Center for Drug Evaluation Research. CDER 2018.
[80]
Hann MM, Leach AR, Harper G. Molecular complexity and its impact on the probability of finding leads for drug discovery. J Chem Inf Comput Sci 2001; 41(3): 856-64.
[http://dx.doi.org/10.1021/ci000403i] [PMID: 11410068]
[81]
Myers S, Baker A. Drug discovery--an operating model for a new era. Nat Biotechnol 2001; 19(8): 727-30.
[http://dx.doi.org/10.1038/90765] [PMID: 11479559]
[82]
DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: new estimates of drug development costs. J Health Econ 2003; 22(2): 151-85.
[http://dx.doi.org/10.1016/S0167-6296(02)00126-1] [PMID: 12606142]
[83]
McAlister FA, Straus S, Sackett D. Randomized clinical trials of antihypertensive drugs: all that glitters is not gold. CMAJ 1998; 159(5): 488-90.
[PMID: 9757173]
[84]
Chakraborty BS. Clinical trials of antihypertensives: Nature of control and design. Indian J Pharmacol 2011; 43(1): 13-7.
[http://dx.doi.org/10.4103/0253-7613.75659] [PMID: 21455414]
[85]
Karaman B, Sippl W. Computational Drug Repurposing: Current Trends. Curr Med Chem 2018; 25.
[PMID: 29848268]
[86]
Katsila T, Spyroulias GA, Patrinos GP, Matsoukas MT. Computational approaches in target identification and drug discovery. Comput Struct Biotechnol J 2016; 14: 177-84.
[http://dx.doi.org/10.1016/j.csbj.2016.04.004] [PMID: 27293534]
[87]
Blundell TL. Structure-based drug design. Nature 1996; 384(6604)(Suppl.): 23-6.
[PMID: 8895597]
[88]
Yousefpour A, Modarress H, Goharpey F, Amjad-Iranagh S. Interaction of PEGylated anti-hypertensive drugs, amlodipine, atenolol and lisinopril with lipid bilayer membrane: A molecular dynamics simulation study. Biochim Biophys Acta 2015; 1848(8): 1687-98.
[http://dx.doi.org/10.1016/j.bbamem.2015.04.016] [PMID: 25960186]
[89]
Wang Z, Cheng LP, Zhang XH, Pang W, Li L, Zhao JL. Design, synthesis and biological evaluation of novel oseltamivir derivatives as potent neuraminidase inhibitors. Bioorg Med Chem Lett 2017; 27(24): 5429-35.
[http://dx.doi.org/10.1016/j.bmcl.2017.11.003] [PMID: 29141777]
[90]
Loganathan L, Muthusamy K. Investigation of Drug Interaction Potentials and Binding Modes on Direct Renin Inhibitors. A Computational Modeling Studies. Lett Drug Des Discov 2018; 15.
[http://dx.doi.org/10.2174/1570180815666180827113622]
[91]
García-Mora P, Martín-Martínez M, Angeles Bonache M, et al. Identification, functional gastrointestinal stability and molecular docking studies of lentil peptides with dual antioxidant and angiotensin I converting enzyme inhibitory activities. Food Chem 2017; 221: 464-72.
[http://dx.doi.org/10.1016/j.foodchem.2016.10.087] [PMID: 27979228]
[92]
Arya H, Syed SB, Singh SS, Ampasala DR, Coumar MS. In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5. Interdiscip Sci 2018; 10(4): 792-804.
[http://dx.doi.org/10.1007/s12539-017-0243-6] [PMID: 28623462]
[93]
Kecel-Gündüz S, Budama-Kilinc Y, Cakir Koc R, et al. Computational design of Phe-tyr dipeptide and preparation, characterization, cytotoxicity studies of Phe-tyr dipeptide loaded PLGA nanoparticles for the treatment of hypertension. J Biomol Struct Dyn 2017; 1102(August): 1-15.
[PMID: 28835169]
[94]
Deng Z, Liu Y, Wang J, et al. Antihypertensive effects of two novel angiotensin I-converting enzyme (ACE) inhibitory peptides from Gracilariopsis lemaneiformis (Rhodophyta) in spontaneously hypertensive rats (SHRs). Mar Drugs 2018; 16(9)E299
[http://dx.doi.org/10.3390/md16090299] [PMID: 30150552]
[95]
Triputra MA, Yanuar A. Analysis of compounds isolated from gnetum gnemon L. Seeds as potential ACE inhibitors through molecular docking and molecular dynamics simulations. J Young Pharm 2018; 10(2s): S32-9.
[http://dx.doi.org/10.5530/jyp.2018.2s.7]
[96]
Walsh CG, Johnson KB. Observational cohort studies and the challenges of in silico experiments. JAMA Oncol 2017; 3(1): 55-7.
[http://dx.doi.org/10.1001/jamaoncol.2016.3478] [PMID: 27737433]
[97]
Singh KD, Muthusamy K. Molecular modeling, quantum polarized ligand docking and structure-based 3D-QSAR analysis of the imidazole series as dual AT(1) and ET(A) receptor antagonists. Acta Pharmacol Sin 2013; 34(12): 1592-606.
[http://dx.doi.org/10.1038/aps.2013.129] [PMID: 24304920]
[98]
Zheng M, Zhao J, Cui C, et al. Computational chemical biology and drug design: Facilitating protein structure, function, and modulation studies. Med Res Rev 2018; 38(3): 914-50.
[http://dx.doi.org/10.1002/med.21483] [PMID: 29323726]
[99]
Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 2014; 46(3): 310-5.
[http://dx.doi.org/10.1038/ng.2892] [PMID: 24487276]
[100]
Karahalil B. Overview of Systems Biology and Omics Technologies. Curr Med Chem 2016; 23(37): 4221-30.
[http://dx.doi.org/10.2174/0929867323666160926150617] [PMID: 27686657]
[101]
Lek M, Karczewski KJ, Minikel EV, et al. Exome Aggregation Consortium. Analysis of protein-coding genetic variation in 60,706 humans. Nature 2016; 536(7616): 285-91.
[http://dx.doi.org/10.1038/nature19057] [PMID: 27535533]
[102]
Singh KhD, Karthikeyan M. Combined sequence and sequence-structure-based methods for analyzing RAAS gene SNPs: a computational approach. J Recept Signal Transduct Res 2014; 34(6): 513-26.
[http://dx.doi.org/10.3109/10799893.2014.922575] [PMID: 24878201]
[103]
Nagamani S, Singh KhD, Muthusamy K. Combined sequence and sequence-structure based methods for analyzing FGF23, CYP24A1 and VDR genes. Meta Gene 2016; 9: 26-36.
[http://dx.doi.org/10.1016/j.mgene.2016.03.005] [PMID: 27114920]
[104]
Wang Z, Moult J. SNPs, protein structure, and disease. Hum Mutat 2001; 17(4): 263-70.
[http://dx.doi.org/10.1002/humu.22] [PMID: 11295823]
[105]
Miller MP, Kumar S. Understanding human disease mutations through the use of interspecific genetic variation. Hum Mol Genet 2001; 10(21): 2319-28.
[http://dx.doi.org/10.1093/hmg/10.21.2319] [PMID: 11689479]
[106]
Sunil K, Giovanna A, Philipp B. SNP2TFBS-a database of regulatory SNPs affecting predicted transcription factor binding site affinity. Nucleic Acids Res 2017; 45(D1): 139-44.
[http://dx.doi.org/10.1093/nar/gkw1064]
[107]
Xiong P, Zhang C, Zheng W, Zhang Y. BindProfX: Assessing mutation-induced binding affinity change by protein interface profiles with pseudo-counts. J Mol Biol 2017; 429(3): 426-34.
[http://dx.doi.org/10.1016/j.jmb.2016.11.022] [PMID: 27899282]
[108]
Jubb HC, Pandurangan AP, Turner MA, Ochoa-Montaño B, Blundell TL, Ascher DB. Mutations at protein-protein interfaces: Small changes over big surfaces have large impacts on human health. Prog Biophys Mol Biol 2017; 128: 3-13.
[http://dx.doi.org/10.1016/j.pbiomolbio.2016.10.002] [PMID: 27913149]
[109]
Patriotis C, Maruvada P, Srivastava S. Molecular Detection and Diagnosis of Cancer. Mol. Basis Hum. Cancer 2016; pp. 797-809.
[110]
Acharya KR, Sturrock ED, Riordan JF, Ehlers MRW. Ace revisited: a new target for structure-based drug design. Nat Rev Drug Discov 2003; 2(11): 891-902.
[http://dx.doi.org/10.1038/nrd1227] [PMID: 14668810]
[111]
Patchett AA, Harris E, Tristram EW, et al. A new class of angiotensin-converting enzyme inhibitors. Nature 1980; 288(5788): 280-3.
[http://dx.doi.org/10.1038/288280a0] [PMID: 6253826]
[112]
von Itzstein M, Wu WY, Kok GB, et al. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 1993; 363(6428): 418-23.
[http://dx.doi.org/10.1038/363418a0] [PMID: 8502295]
[113]
Colman PM, Varghese JN, Laver WG. Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature 1983; 303(5912): 41-4.
[http://dx.doi.org/10.1038/303041a0] [PMID: 6188957]
[114]
Lu X, Yang H, Chen Y, et al. The development of pharmacophore modeling: Generation and recent applications in drug discovery. Curr Pharm Des 2018; 24(29): 3424-39.
[http://dx.doi.org/10.2174/1381612824666180810162944] [PMID: 30101699]

Rights & Permissions Print Cite
Article Metrics
27
1
© 2024 Bentham Science Publishers | Privacy Policy