Abstract
Objective: To screen the phytochemicals for phosphodiesterase 5A (PDE5A) inhibitory potential and identify lead scaffolds of antihypertensive phytochemicals using in silico docking studies.
Methods: In this perspective, reported 269 antihypertensive phytochemicals were selected. Sildenafil, a PDE5A inhibitor was used as the standard. In silico docking study was carried out to screen and identify the inhibiting potential of the selected phytochemicals against PDE5A enzyme using vLife MDS 4.4 software.
Results: Based on docking score, π-stacking, H-bond and ionic interactions, 237 out of 269 molecules were selected which have shown one or more interactions. Protein residue Gln817A was involved in H-boding whereas Val782A, Phe820A and Leu804A were involved in π-stacking interaction with ligand. The selected 237 phytochemicals were structurally diverse, therefore 82 out of 237 molecules with one or more tricycles were filtered out for further analysis. Amongst tricyclic molecules, 14 molecules containing nitrogen heteroatom were selected for lead scaffold identification which finally resulted in three different basic chemical backbones like pyridoindole, tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline as lead scaffolds.
Conclusion: In silico docking studies revealed that nitrogen-containing tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline tricyclic lead scaffolds have emerged as novel PDE5A inhibitors for antihypertensive activity. The identified lead scaffolds may provide antihypertensive lead molecules after its optimization.
Keywords: Antihypertensive, docking, lead scaffold, PDE5A inhibitor, phytochemicals, cardiovascular disease.
Graphical Abstract
[1]
World Health Organization. Global Health Observatory (GHO) data: Reports: World Health Statistics 2017: Monitoring health for the SDGs. www.who.int/gho/publications/world_health_statistics/ 2017/en/ (Accessed June 10, 2018).
[2]
Lackland, D.T.; Weber, M.A. Global burden of cardiovascular disease and stroke: Hypertension at the core. Can. J. Cardiol., 2015, 31(5), 569-571.
[3]
Ferreira, L.G.; Dos Santos, R.N.; Oliva, G.; Andricopulo, A.D. Molecular docking and structure-based drug design strategies. Molecules, 2015, 20(7), 13384-13421.
[4]
Lyne, P.D. Structure-based virtual screening: An overview. Drug Discov. Today, 2002, 7(20), 1047-1055.
[5]
Xiang, L.; Xu, Y.; Zhang, Y.; Meng, X.; Wang, P. Virtual screening studies of chinese medicine Coptidis rhizoma as alpha7 nicotinic acetylcholine receptor agonists for treatment of Alzheimer’s disease. J. Mol. Struct., 2015, 1086, 207-215.
[6]
Prafulla, C.; Manish, B. 3D QSAR, pharmacophore indentification studies on series of 1-(2-ethoxyethyl)-1H-pyrazolo[4,3-d] pyrimidines as PDE5 inhibitors. J. Saudi Chem. Soc., 2015, 19, 265-273.
[7]
Shang, N.N.; Shao, Y.X.; Cai, Y.H.; Guan, M.; Huang, M.; Cui, W.; He, L.; Yu, Y.J.; Huang, L.; Li, Z.; Bu, X.Z.; Ke, H.; Luo, H.B. Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure. Biochem. Pharmacol., 2014, 89(1), 86-98.
[8]
Barone, I.; Giordano, C.; Bonofiglio, D.; Andò, S.; Catalano, S. Phosphodiesterase type 5 and cancers: Progress and challenges. Oncotarget, 2017, 8(58), 99179-99202.
[9]
Konstantinos, G.; Petros, P. Phosphodiesterase-5 inhibitors: Future perspectives. Curr. Pharm. Des., 2009, 15(30), 3540-3551.
[10]
Cristina, R.T.; Cristina, D.; Eugenia, D.; Alina, N.; Gurban, A. Pharmacologic activity of phosphodiesterases and their inhibitors. Lucrari Stiintifice Medicina Veterinara, 2010, XLIII(2), 300-314.
[11]
Bobin, P.; Belacel-Ouari, M.; Bedioune, I.; Zhang, L.; Leroy, J.; Leblais, V.; Fischmeister, R.; Vandecasteele, G. Cyclic nucleotide phosphodiesterases in heart and vessels: A therapeutic perspective. Arch. Cardiovasc. Dis., 2016, 109, 431-443.
[12]
Colombo, G.; Colombo, M.D.H.P.; Schiavon, L.L.; D’Acampora, A.J. Phosphodiesterase 5 as target for adipose tissue disorders. Nitric Oxide, 2013, 35, 186-192.
[13]
Rahimi, R.; Ghiasi, S.; Azimi, H.; Fakhari, S.; Abdollahi, M. A review of the herbal phosphodiesterase inhibitors; future perspective of new drugs. Cytokine, 2010, 49, 123-129.
[14]
Milani, E.; Nikfar, S.; Khorasani, R.; Zamani, M.J.; Abdollahi, M. Reduction of diabetes-induced oxidative stress by phosphodiesterase inhibitors in rats. Comp. Biochem. Physiol. C Toxicol. Pharmacol., 2005, 140, 251-255.
[15]
Mashayekhi, F.; Aghahoseini, F.; Rezaie, A.; Zamani, M.J.; Khorasani, R.; Abdollahi, M. Alteration of cyclic nucleotides levels and oxidative stress in saliva of human subjects with periodontitis. J. Contemp. Dent. Pract., 2005, 6, 46-53.
[16]
Abdollahi, M.; Fooladian, F.; Emami, B.; Zafari, K.; Bahreini-Moghadam, A. Protection by sildenafil and theophylline of lead acetate-induced oxidative stress in rat submandibular gland and saliva. Hum. Exp. Toxicol., 2003, 22, 587-592.
[17]
Domek-Łopacinska, K.; Strosznajder, J.B. The effect of selective inhibition of cyclic GMP hydrolyzing phosphodiesterases 2 and 5 on learning and memory processes and nitric oxide synthase activity in brain during aging. Brain Res., 2008, 1216, 68-77.
[18]
Prickaerts, J.; Sik, A.; van Staveren, W.C.; Koopmans, G.; Steinbusch, H.W.M.; van der Staay, F.J.; Vente, J.; Blokland, A. Phosphodiesterase type 5 inhibition improves early memory consolidation of object information. Neurochem. Int., 2004, 45, 915-928.
[19]
Reneerkens, O.A.; Rutten, K.; Steinbusch, H.W.; Blokland, A.; Prickaerts, J. Selective phosphodiesterase inhibitors: A promising target for cognition enhancement. Psychopharmacology, 2009, 202, 419-443.
[20]
Hamburger, M.; Hostettmann, K. Bioactivity in plants: The link between phytochemistry and medicine. Phytochemistry, 1991, 1212, 3864-3874.
[21]
Schellack, N.; Agoro, A. A review of phosphodiesterase type 5 inhibitors. S. Afr. Fam. Pract., 2014, 56(2), 96-101.
[22]
Makled, S.; Nafee, N.; Boraie, N. Nebulized solid lipid nanoparticles for the potential treatment of pulmonary hypertension via targeted delivery of phosphodiesterase-5-inhibitor. Int. J. Pharm., 2016, 517(1-2), 312-321.
[23]
Ghofrani, H.A.; Wiedemann, R.; Rose, F.; Olschewski, H.; Schermuly, R.T.; Weissmann, N.; Seeger, W.; Grimminger, F. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann. Intern. Med., 2002, 136(7), 515-522.
[24]
Montani, D.; Chaumais, M.C.; Savale, L.; Natali, D.; Price, L.C.; Jais, X.; Humbert, M.; Simonneau, G.; Sitbon, O. Phosphodiesterase type 5 inhibitors in pulmonary arterial hypertension. Adv. Ther., 2009, 26(9), 813-825.
[25]
Wilkens, H.; Guth, A.; Konig, J.; Forestier, N.; Cremers, B.; Hennen, B.; Bohm, M.; Sybrecht, G.W. Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation, 2001, 104(11), 1218-1222.
[26]
Alin, S.; Ronald, T.; Ioan, A.V. Effects of PDE5 inhibitors on endothelial function and cardiovascular autonomic nerve function in men. J. Men’s Health, 2011, 8(2), 109-118.
[27]
Tollefson, M.B.; Acker, B.A.; Jacobsen, E.J.; Hughes, R.O.; Walker, J.K.; Fox, D.N.A.; Palmer, M.J.; Freeman, S.K.; Yu, Y.; Bond, B.R. 1-(2-Ethoxyethyl)-1H-pyrazolo[4,3-d]pyrimidines as potent phosphodiesterase 5 (PDE5) inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(10), 3120-3124.
[28]
Haning, H.; Niewohner, U.; Schenke, T.; Lampe, T.; Hillisch, A.; Bischoff, E. Comparison of different heterocyclic scaffolds as substrate analog PDE5 inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(17), 3900-3907.
[29]
Joshi, J.; Barik, T.K.; Shrivastava, N.; Dimri, M.; Ghosh, S.; Mandal, R.S.; Ramachandran, S.; Kumar, I.P. Cycloxygenase-2 (COX-2) - A potential target for screening of small molecules as radiation countermeasure agents: An in silico study. Curr. Comput. Aided Drug Des., 2013, 9, 35-45.
[30]
Ravindranath, P.A.; Forli, S.; Goodsell, D.S.; Olson, A.J.; Sanner, M.F. AutoDockFR: Advances in protein-ligand docking with explicitly specified binding site flexibility. PLOS Comput. Biol., 2015, 11(12), e1004586.
[31]
Luna-Vázquez, F.J.; Ibarra-Alvarado, C.; Rojas-Molina, A.; Rojas-Molina, I.; Zavala-Sánchez, M.A. Vasodilator compounds derived from plants and their mechanisms of action. Molecules, 2013, 18, 5814-5857.
[32]
Bai, R.R.; Wu, X.M.; Xu, J.Y. Current natural products with antihypertensive activity. Chin. J. Nat. Med., 2015, 13(10), 721-729.
[33]
Tirapelli, C.R.; Ambrosio, S.R.; de Oliveira, A.M.; Tostes, R.C. Hypotensive action of naturally occurring diterpenes: A therapeutic promise for the treatment of hypertension. Fitoterapia, 2010, 81, 690-702.
[34]
Amalraj, A.; Gopi, S. Medicinal properties of Terminalia arjuna (Roxb.) Wight and Arn.: a review. J. Tradit. Complement. Med., 2017, 7(1), 65-78.
[35]
de Souza, P.; Gasparotto, A., Jr; Crestani, S.; Stefanello, M.E.; Marques, M.C.; da Silva-Santos, J.E.; Kassuya, C.A. Hypotensive mechanism of the extracts and artemetin isolated from Achillea millefolium L. (Asteraceae) in rats. Phytomedicine, 2011, 18, 819-825.
[36]
Kamkaew, N.; Scholfield, C.N.; Ingkaninan, K.; Maneesai, P.; Parkington, H.C.; Tare, M.; Chootip, K. Bacopa monnieri and its constituents is hypotensive in anaesthetized rats and vasodilator in various artery types. J. Ethnopharmacol., 2011, 137, 790-795.
[37]
Woolfson, R.G.; Graves, J.; LaBella, F.S.; Templeton, J.F.; Poston, L. Effect of bufalin and pregnanes on vasoreactivity of human resistance arteries. Biochem. Biophys. Res. Commun., 1992, 186(1), 1-7.
[38]
Bhullar, K.S.; Lassalle-Claux, G.; Touaibia, M.; Rupasinghe, H.P. Antihypertensive effect of caffeic acid and its analogs through dual renin-angiotensin-aldosterone system inhibition. Eur. J. Pharmacol., 2014, 730, 125-132.
[39]
Li, Q.Y.; Zhu, Y.F.; Zhang, M.; Chen, L.; Zhang, Z.; Du, Y.L.; Ren, G.Q.; Tang, J.M.; Zhong, M.K.; Shi, X.J. Chlorogenic acid inhibits hypoxia-induced pulmonary artery smooth muscle cells proliferation via c-Src and Shc/Grb2/ERK2 signaling pathway. Eur. J. Pharmacol., 2015, 751, 81-88.
[40]
Gorzalczany, S.; Moscatelli, V.; Ferraro, G. Artemisia copa aqueous extract as vasorelaxant and hypotensive agent. J. Ethnopharmacol., 2013, 148(1), 56-61.
[41]
Sarah, E.A.; Christopher, E.B. The cardiac glycoside convallatoxin inhibits the growth of colorectal cancer cells in a p53-independent manner. Mol. Genet. Metab. Rep., 2017, 13, 42-45.
[42]
Matsuda, H.; Toguchida, I.; Ninomiya, K.; Kageura, T.; Morikawa, T.; Yoshikawa, M. Effects of sesquiterpenes and amino acid-sesquiterpene conjugates from the roots of Saussurea lappa on inducible nitric oxide synthase and heat shock protein in lipopolysaccharide-activated macrophages. Bioorg. Med. Chem., 2003, 11(5), 709-715.
[43]
Ojeda, D.; Jiménez-Ferrer, E.; Zamilpa, A.; Herrera-Arellano, A.; Tortoriello, J.; Alvarez, L. Inhibition of angiotensin convertin enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa. J. Ethnopharmacol., 2010, 127(1), 7-10.
[44]
Nileeka, B.B.W.; Vasantha, R.H.P. Plant flavonoids as angiotensin converting enzyme inhibitors in regulation of hypertension. Functional Foods in Health and Disease, 2011, 1(5), 172-188.
[45]
Chen, K.K.; Elderfield, R.C. The cardiac action of the derivatives of strophanthidin and cymarin. J. Pharmacol. Exp. Ther., 1940, 70, 338-346.
[46]
Senguptaa, B.; Chakraborty, S.; Crawforda, M.; Taylor, J.M.; Blackmona, L.E.; Biswas, P.K.; Kramer, W.H. Characterization of diadzein-hemoglobin binding using optical spectroscopy and molecular dynamics simulations. Int. J. Biol. Macromol., 2012, 51(3), 250-258.
[47]
Ghisalberti, E.L. Cardiovascular activity of naturally occurring lignans. Phytomedicine, 1997, 4(2), 151-166.
[48]
Brown, B.T.; Stafford, A.; Wright, S.E. Chemical structure and pharmacological activity of some derivatives of digitoxigenin and digoxigenin. Br. J. Pharmacol. Chemother., 1962, 18, 311-324.
[49]
Akera, T.; Wiest, S.A.; Brody, T.M. Differential effect of potassium on the action of digoxin and digoxigenin in guinea-pig heart. Eur. J. Pharmacol., 1979, 57(4), 343-351.
[50]
Avila-Villarreal, G.; Hernández-Abreu, O.; Hidalgo-Figueroa, S.; Navarrete-Vázquez, G.; Escalante-Erosa, F.; Pena-Rodríguez, L.M.; Villalobos-Molina, R.; Estrada-Soto, S. Antihypertensive and vasorelaxant effects of dihydrospinochalcone-A isolated from Lonchocarpus xuul Lundell by NO production: Computational and ex vivo approaches. Phytomedicine, 2013, 20, 1241-1246.
[51]
Suzuki, A.; Yamamoto, M.; Jokura, H.; Fujii, A.; Tokimitsu, I.; Hase, T.; Saito, I. Ferulic acid restores endothelium-dependent vasodilation in aortas of spontaneously hypertensive rats. Am. J. Hypertens., 2007, 20(5), 508-513.
[52]
Vaden, S.L.; Adams, H.R. Inotropic, chronotropic and coronary vasodilator potency of forskolin. Eur. J. Pharmacol., 1985, 118(1-2), 131-137.
[53]
Yun, H.M.; Ban, J.O.; Park, K.R.; Lee, C.K.; Jeong, H.S.; Han, S.B.; Hong, J.T. Potential therapeutic effects of functionally active compounds isolated from garlic. Pharmacol. Ther., 2014, 142(2), 183-195.
[54]
Mohanan, P.; Subramaniyam, S.; Mathiyalagan, R.; Yang, D.C. Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions. J. Ginseng Res., 2018, 42(2), 123-132.
[55]
Lee, K.H.; Bae, I.Y.; Park, S.I.; Park, J.D.; Lee, H.G. Antihypertensive effect of Korean red ginseng by enrichment of ginsenoside Rg3 and arginine-fructose. J. Ginseng Res., 2016, 40(3), 237-244.
[56]
Haustein, K.O.; Markwardt, F.; Repke, K.R. Different relationships between therapeutic and toxic actions of 16-epi-gitoxin, gitoxin and ouabain on isolated cardiac preparations. Eur. J. Pharmacol., 1970, 10(1), 1-10.
[57]
Hügel, H.; Jackson, N.; May, B.; Zhang, A.L.; Xue, C.C. Polyphenol protection and treatment of hypertension. Phytomedicine, 2016, 23, 220-231.
[58]
Inchoo, M.; Chirdchupunseree, H.; Pramyothin, P.; Jianmongkol, S. Endothelium-independent effects of phyllanthin and hypophyllanthin on vascular tension. Fitoterapia, 2011, 82(8), 1231-1236.
[59]
Arora, R.B.; Arora, C.K.E. In: Pharmacology of Oriental Plants,Proceedings of the 1st International Pharmacological Meeting, Stockholm, SwedenAugust 22-25, 1961Chen, K.K., Mukerji, B. Eds.; Elsevier Science B.V: Amsterdam, . 1965, pp. 51-60.
[60]
Somova, L.I.; Shode, F.O.; Moodley, K.; Govender, Y. Cardiovascular and diuretic activity of kaurene derivatives of Xylopia aethiopica and Alepidea amatymbica. J. Ethnopharmacol., 2001, 77, 165-174.
[61]
Tay, A.; Özçelikay, A.T.; Altan, V.M. Effects of L-arginine on blood pressure and metabolic changes in fructose-hypertensive rats. Am. J. Hypertens., 2002, 15(1), 72-77.
[62]
Gracey, D.R.; Brandfonbrener, M. The effect of lanatoside C on coronary vascular resistance. Am. Heart J., 1963, 66(1), 88-94.
[63]
Lavín de Juan, L.; García Recio, V.; Jiménez López, P.; Girbés Juan, T.; Cordoba-Diaz, M.; Cordoba-Diaz, D. Pharmaceutical applications of lectins. J. Drug Deliv. Sci. Technol., 2017, 42, 126-133.
[64]
Hansen, K.; Adsersen, A.; Christensen, S.B.; Jensen, S.R.; Nyman, U.; Smiti, U.W. Isolation of an angiotensin converting enzyme (ACE) inhibitor from Olea europaea and Olea lancea. Phytomedicine, 1996, 2(4), 319-325.
[65]
Bouaziz, A.; Khennouf, S.; Zarga, M.A.; Abdalla, S.; Baghiani, A.; Charef, N. Phytochemical analysis, hypotensive effect and antioxidant properties of Myrtus communis L. growing in Algeria. Asian Pac. J. Trop. Biomed., 2015, 5(1), 19-28.
[66]
Patel, S. Plant-derived cardiac glycosides: Role in heart ailments and cancer management. Biomed. Pharmacother., 2016, 84, 1036-1041.
[67]
Lopez-Carreras, N.; Castillo, J.; Muguerza, B.; Aleixandre, A. Endothelium-dependent vascular relaxing effects of different citrus and olive extracts in aorta rings from spontaneously hypertensive rats. Food Res. Int., 2015, 77(3), 484-490.
[68]
Blaustein, M.P.; Hamlyn, J.M. Signaling mechanisms that link salt retention to hypertension: Endogenous ouabain, the Na(+) pump, the Na(+)/Ca(2+) exchanger and TRPC proteins. Biochim. Biophys. Acta, 2010, 1802(12), 1219-1229.
[69]
Jimmy, D.O.; Priyanka, P. Antihypertensive activity of bamboo shoot: A review. Asian J. Pharm. Clin. Res., 2015, 8(1), 46-47.
[70]
Ferreira, L.G.; Evora, P.R.B.; Capellini, V.K.; Albuquerque, A.A.; Carvalho, M.T.M.; Gomes, R.A.D.S.; Parolini, M.T.; Celotto, A.C. Effect of rosmarinic acid on the arterial blood pressure in normotensive and hypertensive rats: Role of ACE. Phytomedicine, 2018, 38, 158-165.
[71]
Ferrari, P. Rostafuroxin: An ouabain-inhibitor counteracting specific forms of hypertension. Biochim. Biophys. Acta, 2010, 1802(12), 1254-1258.
[72]
Lei, Z.H.; Jin, Z.X.; Ma, Y.L.; Tai, B.S.; Kong, Q.; Yaharaa, S.; Nohara, T. Cardiac glycosides from Erysimum cheiranthoides. Phytochemistry, 1998, 49(6), 1801-1803.
[73]
Shang, Q.; Xu, H.; Huang, L. Tanshinone IIA: A promising natural cardioprotective agent. Evid. Based Complement. Alternat. Med., 2012, 2012(7), 1-7.
[74]
Saravanakumar, M.; Raja, B. Veratric acid, a phenolic acid attenuates blood pressure and oxidative stress in L-NAME induced hypertensive rats. Eur. J. Pharmacol., 2011, 671(1-3), 87-94.
[75]
Singh, A.; Duggal, S.; Suttee, A.; Singh, J.; Katekhaye, S. Eclpita alba Linn. - ancient remedy with therapeutic potential. Int. J. Phytopharmacology, 2010, 1(2), 57-63.
[76]
Meenu, H.C.; Sokindra, K. Ajeet. Eclipta alba, a bunch of pharmacological possibilities- a review. Mod. Appl. Bioequiv. Availab., 2017, 2(1), 1-6.
[77]
Murali, B.; Amit, A.; Anand, M.S.; Samiulla, D.S. Estimation of wedelolactone and demethylwedelolactone in Eclipta alba Hassk. by improved chromatograhic analysis. J. Nat. Rem., 2002, 2(1), 99-201.
[78]
Sawant, S.D.; Reddy, G.L.; Dar, M.I.; Srinivas, M.; Gupta, G.; Sahu, P.K.; Mahajan, P.; Nargotra, A.; Singh, S.; Sharma, S.C.; Tikoo, M.; Singh, G.; Vishwakarma, R.A.; Syed, S.H. Discovery of novel pyrazolopyrimidinone analogs as potent inhibitors of phosphodiesterase type-5. Bioorg. Med. Chem., 2015, 23, 2121-2128.
[79]
Madeswaran, A.; Umamaheswari, M.; Asokkumar, K.; Sivashanmugam, T.; Subhadradevi, V.; Jagannath, P. Computational drug discovery of potential phosphodiesterase inhibitors using in silico studies. Asian Pac. J. Trop. Dis., 2012, 2(2), S822-S826.
[80]
Mohamad, R.M.N.; Mohd, A.S.; Abu Bakar, M.H.; Razali, S.A.; Mohamed, Z.R.; Ya’akob, H. Molecular docking studies of bioactive compounds from Annona muricata Linn as potential inhibitors for Bcl-2, Bcl-w and Mcl-1 antiapoptotic proteins. Apoptosis, 2018, 23(1), 27-40.
[81]
Abusnina, A.; Lugnier, C. Therapeutic potentials of natural compounds acting on cyclic nucleotide phosphodiesterase families. Cell. Signal., 2017, 39, 55-65.
[82]
Yu, S.M.; Cheng, Z.J.; Kuo, S.C. Endothelium-dependent relaxation of rat aorta by butein, a novel cyclic AMP-specific phosphodiesterase inhibitor. Eur. J. Pharmacol., 1995, 280(1), 69-77.
[83]
Gonçalves, R.L.; Lugnier, C.; Keravis, T.; Lopes, M.J.; Fantini, F.A.; Schmitt, M.; Cortes, S.F.; Lemos, V.S. The flavonoid dioclein is a selective inhibitor of cyclic nucleotide phosphodiesterase type 1 (PDE1) and a cGMP-dependent protein kinase (PKG) vasorelaxant in human vascular tissue. Eur. J. Pharmacol., 2009, 620(1-3), 78-83.
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