Synthesis and Biological Activity of a Bis-steroid-methanocyclobutanaphthalene- dione Derivative against Ischemia/Reperfusion Injury via Calcium Channel Activation

Author(s): Figueroa-Valverde Lauro*, Diaz-Cedillo Francisco, Rosas-Nexticapa Marcela*, Mateu-Armand Virginia, Garcimarero-Espino E. Alejandra, Lopez-Ramos Maria, Hau-Heredia Lenin, Borges-Ballote Yaritza, Cabrera-Tuz Jhair

Journal Name: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Formerly Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents

Volume 19 , Issue 4 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: There is some experimental data on the effect exerted by some steroid derivatives against ischemia/reperfusion injury; however, the molecular mechanism is very confusing, perhaps this phenomenon could be due to the protocols used and/or differences in the chemical structure of each one of the steroid derivatives.

Objectives: The aim of this study was to synthesize a new bis-steroid-methanocyclobutanaphthalene- dione derivative using some tools chemical.

Methodology: The biological activity exerted by the bis-steroid-methanocyclobutanaphthalene- dione derivative against ischemia/reperfusion injury was evaluated in an isolated heart model using noradrenaline, milrinone, dobutamine, levosimendan, and Bay-K- 8644 as controls. In addition, other alternative experiments were carried out to evaluate the biological activity induced by the bis-steroid-methanocyclobuta-naphthalene-dione derivative against left ventricular pressure in the absence or presence of nifedipine.

Results: The results showed that 1) the bis-steroid-methanocyclobuta-naphthalene-dione derivative significantly decreases the ischemia-reperfusion injury translated as a decrease in the the infarct area in a similar manner to levosimendan drug; 2) both bis-steroidmethanocyclobuta- naphthalene-dione and Bay-K-8644 increase the left ventricular pressure and 3) the biological activity exerted by bis-steroid-methanocyclobuta-naphthalenedione derivative against left ventricular pressure is inhibited by nifedipine.

Conclusion: In conclusion, the bis-steroid-methanocyclobuta-naphthalene-dione derivative decreases the area of infarction and increases left ventricle pressure via calcium channels activation; this phenomenon could constitute a new therapy for ischemia/reperfusion injury.

Keywords: Infarct, ischemia, pressure, reperfusion, steroid, calcium channel.

[1]
Maida, C.; Tuttolomondo, A.; Di Raimondo, D.; Daidone, M.; Pinto, A. Management of blood pressure and heart rate in patients with acute stroke. Curr. Pharm. Des., 2017, 23(31), 4583-4597.
[http://dx.doi.org/10.2174/1381612823666170714162455] [PMID: 28714410]
[2]
Thygesen, K.; Alpert, J.S.; Jaffe, A.S.; Chaitman, B.R.; Bax, J.J.; Morrow, D.A.; White, H.D. Fourth universal definition of myocardial infarction. J. Am. Coll. Cardiol., 2018, 72(18), 2231-2264.
[http://dx.doi.org/10.1016/j.jacc.2018.08.1038] [PMID: 30153967]
[3]
Pfeffer, M.A. Left ventricular remodeling after acute myocardial infarction. Annu. Rev. Med., 1995, 46, 455-466.
[http://dx.doi.org/10.1146/annurev.med.46.1.455] [PMID: 7598478]
[4]
Klone, R.; Przyklener, K.; Whittaker, P. Deterious effects of oxygen radicals in ischemia/reperfusion. Circulation, 1989, 80, 1115-1127.
[http://dx.doi.org/10.1161/01.CIR.80.5.1115]
[5]
Rasmussen, H.H.; Okita, G.T.; Hartz, R.S.; ten Eick, R.E. Inhibition of electrogenic Na(+)-pumping in isolated atrial tissue from patients treated with digoxin. J. Pharmacol. Exp. Ther., 1990, 252(1), 60-64.
[PMID: 2299603]
[6]
Sundberg, S.; Lilleberg, J.; Nieminen, M.S.; Lehtonen, L. Hemodynamic and neurohumoral effects of levosimendan, a new calcium sensitizer, at rest and during exercise in healthy men. Am. J. Cardiol., 1995, 75(15), 1061-1066.
[http://dx.doi.org/10.1016/S0002-9149(99)80725-5] [PMID: 7747690]
[7]
Ruffolo, R.R., Jr The pharmacology of dobutamine. Am. J. Med. Sci., 1987, 294(4), 244-248.
[http://dx.doi.org/10.1097/00000441-198710000-00005] [PMID: 3310640]
[8]
Silver, P.J.; Lepore, R.E.; O’Connor, B.; Lemp, B.M.; Hamel, L.T.; Bentley, R.G.; Harris, A.L. Inhibition of the low Km cyclic AMP phosphodiesterase and activation of the cyclic AMP system in vascular smooth muscle by milrinone. J. Pharmacol. Exp. Ther., 1988, 247(1), 34-42.
[PMID: 2845058]
[9]
Pfeffer, M.A.; McMurray, J.J.; Velazquez, E.J.; Rouleau, J.L.; Køber, L.; Maggioni, A.P.; Solomon, S.D.; Swedberg, K.; Van de Werf, F.; White, H.; Leimberger, J.D.; Henis, M.; Edwards, S.; Zelenkofske, S.; Sellers, M.A.; Califf, R.M. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N. Engl. J. Med., 2003, 349(20), 1893-1906.
[http://dx.doi.org/10.1056/NEJMoa032292] [PMID: 14610160]
[10]
Struthers, A.; Krum, H.; Williams, G.H. A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin. Cardiol., 2008, 31(4), 153-158.
[http://dx.doi.org/10.1002/clc.20324] [PMID: 18404673]
[11]
Figueroa-Valverde, L.; Díaz-Cedillo, F.; López-Ramos, M.; García-Cervera, E.; Quijano-Ascencio, K. [Inotropic activity induced by carbamazepine-alkyne derivative in an isolated heart model and perfused to constant flow Biomedica, 2011, 31(2), 232-241.
[http://dx.doi.org/10.7705/biomedica.v31i2.310] [PMID: 22159540]
[12]
Follmann, M.; Ackerstaff, J.; Redlich, G.; Wunder, F.; Lang, D.; Kern, A.; Fey, P.; Griebenow, N.; Kroh, W.; Becker-Pelster, E.M.; Kretschmer, A.; Geiss, V.; Li, V.; Straub, A.; Mittendorf, J.; Jautelat, R.; Schirok, H.; Schlemmer, K.H.; Lustig, K.; Gerisch, M.; Knorr, A.; Tinel, H.; Mondritzki, T.; Trübel, H.; Sandner, P.; Stasch, J.P. Discovery of the soluble guanylate cyclase stimulator vericiguat (BAY 1021189) for the treatment of chronic heart failure. J. Med. Chem., 2017, 60(12), 5146-5161.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00449] [PMID: 28557445]
[13]
Sircar, I.; Steffen, R.P.; Bobowski, G.; Burke, S.E.; Newton, R.S.; Weishaar, R.E.; Bristol, J.A.; Evans, D.B. Cardiotonic agents. 9. Synthesis and biological evaluation of a series of (E)-4,5-dihydro-6-[2-[4-(1H-imidazol-1-yl)phenyl]ethenyl]-3 (2H)-pyridazinones: a novel class of compounds with positive inotropic, antithrombotic, and vasodilatory activities for the treatment of congestive heart failure. J. Med. Chem., 1989, 32(2), 342-350.
[http://dx.doi.org/10.1021/jm00122a011] [PMID: 2536438]
[14]
Zhang, R.; Lei, L.; Xu, Y.G.; Hua, W.Y.; Gong, G.Q. Benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines as novel Na+/H+ exchanger inhibitors, synthesis and protection against ischemic-reperfusion injury. Bioorg. Med. Chem. Lett., 2007, 17(9), 2430-2433.
[http://dx.doi.org/10.1016/j.bmcl.2007.02.035] [PMID: 17346962]
[15]
Jawan, B.; Goto, S.; Pan, T.L.; Lai, C.Y.; Luk, H.N.; Eng, H.L.; Lin, Y.C.; Chen, Y.S.; Lan, K.M.; Hsieh, S.W.; Wang, C.C.; Cheng, Y.F.; Chen, C.L. The protective mechanism of magnolol, a Chinese herb drug, against warm ischemia-reperfusion injury of rat liver. J. Surg. Res., 2003, 110(2), 378-382.
[http://dx.doi.org/10.1016/S0022-4804(03)00034-9] [PMID: 12788668]
[16]
Hale, S.L.; Birnbaum, Y.; Kloner, R.A. β-Estradiol, but not α-estradiol, reduced myocardial necrosis in rabbits after ischemia and reperfusion. Am. Heart J., 1996, 132(2 Pt 1), 258-262.
[http://dx.doi.org/10.1016/S0002-8703(96)90419-6] [PMID: 8701884]
[17]
Kim, Y.D.; Chen, B.; Beauregard, J.; Kouretas, P.; Thomas, G.; Farhat, M.Y.; Myers, A.K.; Lees, D.E. 17 β-Estradiol prevents dysfunction of canine coronary endothelium and myocardium and reperfusion arrhythmias after brief ischemia/reperfusion. Circulation, 1996, 94(11), 2901-2908.
[http://dx.doi.org/10.1161/01.CIR.94.11.2901] [PMID: 8941119]
[18]
Dhote, V.V.; Balaraman, R. Gender specific effect of progesterone on myocardial ischemia/reperfusion injury in rats. Life Sci., 2007, 81(3), 188-197.
[http://dx.doi.org/10.1016/j.lfs.2007.05.010] [PMID: 17585947]
[19]
Suparto, I.H.; Koudy Williams, J.; Fox, J.L.; Vinten-Johansen, J. A comparison of two progestins on myocardial ischemia-reperfusion injury in ovariectomized monkeys receiving estrogen therapy. Coron. Artery Dis., 2005, 16(5), 301-308.
[http://dx.doi.org/10.1097/00019501-200508000-00007] [PMID: 16000888]
[20]
Jeanes, H.L.; Wanikiat, P.; Sharif, I.; Gray, G.A. Medroxyprogesterone acetate inhibits the cardioprotective effect of estrogen in experimental ischemia-reperfusion injury. Menopause, 2006, 13(1), 80-86.
[http://dx.doi.org/10.1097/01.gme.0000196593.44335.eb] [PMID: 16607102]
[21]
Figueroa, L.; Díaz, F.; Rosas, M.; Mateu, V. Design and synthesis of two steroid derivatives from 2-nitroestrone and theoretical evaluation of their interaction with BRCA-1. Asian J. Green Chem., 2019, 3, 216-235.
[22]
Şahin, A.D.; Saçan, M.T. Understanding the toxic potencies of xenobiotics inducing TCDD/TCDF-like effects. SAR QSAR Environ. Res., 2018, 29(2), 117-131.
[http://dx.doi.org/10.1080/1062936X.2017.1414075] [PMID: 29308921]
[23]
Tahir, M.; Khalid, M.; Islam, A.; Mashhadi, S.; Braga, A. Facile synthesis, single crystal analysis, and computational studies of sulfanilamide derivatives. J. Mol. Struct., 2017, 1127, 766-776.
[http://dx.doi.org/10.1016/j.molstruc.2016.08.032]
[24]
Hartman, A.M.; Hirsch, A.K.H. Molecular insight into specific 14-3-3 modulators: inhibitors and stabilisers of protein-protein interactions of 14-3-3. Eur. J. Med. Chem., 2017, 136, 573-584.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.058] [PMID: 28549334]
[25]
Wolber, G.; Langer, T. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J. Chem. Inf. Model., 2005, 45(1), 160-169.
[http://dx.doi.org/10.1021/ci049885e] [PMID: 15667141]
[26]
Réau, M.; Langenfeld, F.; Zagury, J.F.; Montes, M. Predicting the affinity of Farnesoid X Receptor ligands through a hierarchical ranking protocol: a D3R Grand Challenge 2 case study. J. Comput. Aided Mol. Des., 2018, 32(1), 231-238.
[http://dx.doi.org/10.1007/s10822-017-0063-0] [PMID: 28913743]
[27]
Valverde, L.F.; Cedillo, F.D.; Ramos, M.L.; Cervera, E.G.; Quijano, K.; Cordoba, J. Changes induced by estradiol-ethylenediamine derivative on perfusion pressure and coronary resistance in isolated rat heart: L-type calcium channel. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2011, 155(1), 27-32.
[http://dx.doi.org/10.5507/bp.2011.018] [PMID: 21475374]
[28]
Figueroa-Valverde, L.; Marcela, R.; Virginia, M.; Socorro, H.; Francisco, D.; Elodia, G. Evaluation of biological activity exerted by an Aza-Bicyclo-carboxylic acid derivative using an ischemia-reperfusion injury model. Biomed. Pharmacol. J., 2018, 11(4), 1865-1877.
[http://dx.doi.org/10.13005/bpj/1559]
[29]
Figueroa, L.; Diaz, F.; Rosas, M.; Pool, E.; Lopez, M.; Sarabia, B.; Damian, I. Evaluation of activity exerted by a steroid derivative on injury by ischaemia/reperfusion. Afr. J. Pharm. Pharmacol., 2014, 8, 157-167.
[http://dx.doi.org/10.5897/AJPP2013.3908]
[30]
Hocht, C.; Opezzo, J.; Gorzalczany, S.; Bramuglia, G.; Tiara, C. Una aproximación cinética y dinámica de metildopa en ratas con coartación aórtica mediante microdiálisis. Rev. Argent. Cardiol., 1999, 67, 769-773.
[31]
Suresh, P.K.; Divya, N.; Nidhi, S.; Rajasekaran, R. Phenytoin-Bovine Serum Albumin interactions - modeling plasma protein- drug binding: A multi-spectroscopy and in silico-based correlation. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2018, 193, 523-527.
[http://dx.doi.org/10.1016/j.saa.2017.12.069] [PMID: 29304487]
[32]
Askar, I.; Bozkurt, M. Protective effects of immunosuppressants and steroids against ischemia-reperfusion injury in cremaster muscle flap at microcirculatory level. Microsurgery, 2002, 22(8), 361-366.
[http://dx.doi.org/10.1002/micr.10071] [PMID: 12497573]
[33]
Martens, A.; Boada, M.; Vanaudenaerde, B.M.; Verleden, S.E.; Vos, R.; Verleden, G.M.; Verbeken, E.K.; Van Raemdonck, D.; Schols, D.; Claes, S.; Neyrinck, A.P. Steroids can reduce warm ischemic reperfusion injury in a porcine donation after circulatory death model with ex vivo lung perfusion evaluation. Transpl. Int., 2016, 29(11), 1237-1246.
[http://dx.doi.org/10.1111/tri.12823] [PMID: 27514498]
[34]
Gabel, S.A.; Walker, V.R.; London, R.E.; Steenbergen, C.; Korach, K.S.; Murphy, E. Estrogen receptor beta mediates gender differences in ischemia/reperfusion injury. J. Mol. Cell. Cardiol., 2005, 38(2), 289-297.
[http://dx.doi.org/10.1016/j.yjmcc.2004.11.013] [PMID: 15698835]
[35]
Kam, K.W.; Qi, J.S.; Chen, M.; Wong, T.M. Estrogen reduces cardiac injury and expression of β1-adrenoceptor upon ischemic insult in the rat heart. J. Pharmacol. Exp. Ther., 2004, 309(1), 8-15.
[http://dx.doi.org/10.1124/jpet.103.058339] [PMID: 14718598]
[36]
Das, B.; Sarkar, C. Similarities between ischemic preconditioning and 17β-estradiol mediated cardiomyocyte KATP channel activation leading to cardioprotective and antiarrhythmic effects during ischemia/reperfusion in the intact rabbit heart. J. Cardiovasc. Pharmacol., 2006, 47(2), 277-286.
[http://dx.doi.org/10.1097/01.fjc.0000202563.54043.d6] [PMID: 16495767]
[37]
Lee, T.M.; Lin, M.S.; Chou, T.F.; Tsai, C.H.; Chang, N.C. Adjunctive 17β-estradiol administration reduces infarct size by altered expression of canine myocardial connexin43 protein. Cardiovasc. Res., 2004, 63(1), 109-117.
[http://dx.doi.org/10.1016/j.cardiores.2004.03.009] [PMID: 15194467]
[38]
Smith, S.W.; Newman, M.S. The gem-dialkyl effect. II. A comparison of the kinetic and equilibrium approaches to the selective ketalization of 5 alpha-androstane-3,17-dione with various glycols. J. Am. Chem. Soc., 1968, 90(5), 1249-1253.
[http://dx.doi.org/10.1021/ja01007a025] [PMID: 5636535]
[39]
Jia, P.; Wu, X.; Yu, Y.; Zhang, G. An efficient one-pot synthesis of 5, 9-cyclo-1, 11-oxido-pregn-16-ene-3, 20-dione from 9-bromide-11-hydroxypregna-1, 4, 16-trien-3, 20-dione by two annulation reactions. Steroids, 2009, 74(2), 229-232.
[http://dx.doi.org/10.1016/j.steroids.2008.10.018] [PMID: 19041660]
[40]
Hunter, A.C.; Priest, S.M. An efficient one-pot synthesis generating 4-ene-3,6-dione functionalised steroids from steroidal 5-en-3β-ols using a modified Jones oxidation methodology. Steroids, 2006, 71(1), 30-33.
[http://dx.doi.org/10.1016/j.steroids.2005.07.007] [PMID: 16183090]
[41]
Takekoshi, T. Synthesis of high-performance aromatic polymers via nucleophilic nitro displacement reaction. Polym. J., 1987, 19, 191-202.
[http://dx.doi.org/10.1295/polymj.19.191]
[42]
Traesel, H.J.; Olivato, P.R.; Rodrigues, D.N.S.; Valença, J.; Rodrigues, A.; Zukerman-Schpector, J.; Colle, M.D. Spectroscopic and theoretical studies of some 2-(methoxy)-2-[(4-substituted)-phenylsulfanyl]-(4′-substituted) acetophenones. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2019, 210, 82-97.
[http://dx.doi.org/10.1016/j.saa.2018.11.010] [PMID: 30447629]
[43]
Wenlock, M.C.; Austin, R.P.; Barton, P.; Davis, A.M.; Leeson, P.D. A comparison of physiochemical property profiles of development and marketed oral drugs. J. Med. Chem., 2003, 46(7), 1250-1256.
[http://dx.doi.org/10.1021/jm021053p] [PMID: 12646035]
[44]
Brocos, P.; Piñeiro, Á.; Bravo, R.; Amigo, A. Refractive indices, molar volumes and molar refractions of binary liquid mixtures: concepts and correlations. Phys. Chem. Chem. Phys., 2003, 5(3), 550-557.
[http://dx.doi.org/10.1039/b208765k]
[45]
Aminabhavi, T. A simple theory to predict small changes in volume and refractivity during mixing of a two-component liquid system. J. Chem. Educ., 1983, 60, 117.
[http://dx.doi.org/10.1021/ed060p117]
[46]
Fleming, F.F.; Yao, L.; Ravikumar, P.C.; Funk, L.; Shook, B.C. Nitrile-containing pharmaceuticals: efficacious roles of the nitrile pharmacophore. J. Med. Chem., 2010, 53(22), 7902-7917.
[http://dx.doi.org/10.1021/jm100762r] [PMID: 20804202]
[47]
Richardt, G.; Waas, W.; Kranzhöfer, R.; Mayer, E.; Schömig, A. Adenosine inhibits exocytotic release of endogenous noradrenaline in rat heart: a protective mechanism in early myocardial ischemia. Circ. Res., 1987, 61(1), 117-123.
[http://dx.doi.org/10.1161/01.RES.61.1.117] [PMID: 3608108]
[48]
Lilleberg, J.; Sundberg, S.; Nieminen, M.S. Dose-range study of a new calcium sensitizer, levosimendan, in patients with left ventricular dysfunction. J. Cardiovasc. Pharmacol., 1995, 26(Suppl. 1), S63-S69.
[http://dx.doi.org/10.1097/00005344-199506261-00009] [PMID: 8907133]
[49]
Wang, J.; Yang, H.; Hu, X.; Fu, W.; Xie, J.; Zhou, X.; Xu, W.; Jiang, H. Dobutamine-mediated heme oxygenase-1 induction via PI3K and p38 MAPK inhibits high mobility group box 1 protein release and attenuates rat myocardial ischemia/reperfusion injury in vivo. J. Surg. Res., 2013, 183(2), 509-516.
[http://dx.doi.org/10.1016/j.jss.2013.02.051] [PMID: 23531454]
[50]
Du Toit, E.F.; Muller, C.A.; McCarthy, J.; Opie, L.H. Levosimendan: effects of a calcium sensitizer on function and arrhythmias and cyclic nucleotide levels during ischemia/reperfusion in the Langendorff perfused guinea pig heart. J. Pharmacol. Exp. Ther., 1999, 290(2), 505-514.
[PMID: 10411556]
[51]
Papp, J.G.; Pollesello, P.; Varró, A.F.; Végh, A.S. Effect of levosimendan and milrinone on regional myocardial ischemia/reperfusion-induced arrhythmias in dogs. J. Cardiovasc. Pharmacol. Ther., 2006, 11(2), 129-135.
[http://dx.doi.org/10.1177/1074248406289286] [PMID: 16891290]
[52]
García, A.G.; Sala, F.; Reig, J.A.; Viniegra, S.; Frías, J.; Fontériz, R.; Gandía, L. Dihydropyridine BAY-K-8644 activates chromaffin cell calcium channels. Nature, 1984, 309(5963), 69-71.
[http://dx.doi.org/10.1038/309069a0] [PMID: 6201747]
[53]
Bortolato, A.; Deflorian, F.; Weiss, D.R.; Mason, J.S. Decoding the role of water dynamics in ligand–protein unbinding: CRF1R as a test case. J. Chem. Inf. Model., 2015, 55(9), 1857-1866.
[http://dx.doi.org/10.1021/acs.jcim.5b00440] [PMID: 26335976]
[54]
Berman, H.; Henrick, K.; Nakamura, H.; Markley, J.L. The worldwide Protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data. Nucleic Acids Res., 2007, 35(Database issue), D301-D303.
[http://dx.doi.org/10.1093/nar/gkl971] [PMID: 17142228]
[55]
Figueroa-Valverde, L.; Rosas-Nexticapa, M.; Mateu-Armand, V.; Diaz-Cedillo, F.; Lenin, H.; Lopez-Ramos, M.; Regina, C. Preparation of two cyclobutadiene-steroid derivatives. Theoretical analysis of its interaction with the µ, δ, and k opiod-receptors. Orient. J. Chem., 2018, 34(6), 2689-2702.
[http://dx.doi.org/10.13005/ojc/340601]


open access plus

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 4
Year: 2020
Published on: 15 October, 2020
Page: [393 - 412]
Pages: 20
DOI: 10.2174/1871523018666191003152854

Article Metrics

PDF: 29
HTML: 2
EPUB: 1
PRC: 1