Synthesis of two 7,8-dioxabicyclo[4.1.1]octan-3-yl)-steroid derivatives and evaluation of their inotropic activity in an animal model.

Year 2020, Volume: 48 Issue: 1, 1 - 12, 17.04.2020

Figueroa Lauro Lopez Marıa Diaz Francısco Rosas Marcela Mateu Vırgınıa Garcimarrero Alejandra Borges Yarıtza

https://doi.org/10.15671/hjbc.602029

Cited By: 1

Abstract

The aim of this study was synthesizing two 7,8-dioxabicyclo[4.1.1]octan-3-yl)-steroid derivatives (compounds 3 or 4) to evaluate their inotropic activity in vitro. The first stage was achieved by the preparation of two 7,8-dioxabicyclo[4.1.1]octan-3-yl)-steroid derivatives using some chemical strategies. Then, the inotropic activity of both steroid derivatives against left ventricular pressure (LVP) was evaluated in an isolated rat heart model using Bay-k-8644, nifedipine, aucubin, and L-NAME as controls. The results showed that compound 3 increased LVP in a dose-dependent manner and this effect was inhibited by nifedipine. Other results showed that compound 4 decreased LVP in a dose-dependent manner and this effect was blocked in the presence of L-NAME. All these data indicate that 1) the positive inotropic activity exerted by compound 3 was through type L calcium channel activation; 2) the negative inotropic effect of 4 was via nitric oxide synthase activation. These phenomena could be due to the different functional groups involved in the chemical structure of compounds 3 and 4.

Keywords

Steroid, dioxabicyclo, inotropic

Supporting Institution

University Autonomous of Campeche

References

• 1. K.K. Ho, J.L. Pinsky, W.B. Kannel, D. Levy, The epidemiology of heart failure: the Framingham Study, J. Am. Coll. Cardiol., 22 (1993) A6-A13.2. J.J. McMurray, S. Adamopoulos, S.D. Anker, A. Auricchio, M. Böhm, M. Gomez, ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC, Eur J Heart Fail., 14 (2012) 803-869.3. B. Pitt, F. Zannad, W.J. Remme, R. Cody, A. Castaigne, A. Perez, J. Wittes, The effect of spironolactone on morbidity and mortality in patients with severe heart failure, N Eng J Med., 341 (1999) 709-717.4. Digitalis Investigation Group, The effect of digoxin on mortality and morbidity in patients with heart failure, N Eng J Med., 336 (1999) 525-533.5. M.A. Pfeffer, J.J. McMurray, E.J. Velazquez, J.L. Rouleau, L. Køber, A.P. Maggioni, J.D. Leimberger, Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both, N Eng J Med., 349 (2003) 1893-1906.6. J.N. Cohn, G. Tognoni, A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure, N Eng J Med., 345 (2001) 1667-1675.7. A. Mebazaa, M.S. Nieminen, M. Packer, A. Cohen-Solal, Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial, J Am Med Assoc., 297 (2007) 1883-1891.8. M. Kivikko, S. Antila, J. Eha, L. Lehtonen, P. Pentikäinen, Pharmacodynamics and safety of a new calcium sensitizer, levosimendan, and its metabolites during an extended infusion in patients with severe heart failure, J. Clin. Pharmacol., 2 (2002) 43-51.9. D. Baim, A. McDowell, J. Cherniles, E. Monrad, A. Parker, J. Edelson, W. Grossman, Evaluation of a new bipyridine inotropic agent-milrinone in patients with severe congestive heart failure, N Engl J Med., 309 (1983) 748-75610. M.R. Rose, E. Glassma, F.C. Spencer, Arrhythmias following cardiac surgery: relation to serum digoxin levels, Am Heart J., 89 (1975) 288-294.11. K. Silberbauer, B. Stanek, H. Templ, Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition, Br J Clin Pharmacol., 14 (1982) 87S-93S12. D.J. Greenblatt, J. Koch-Weser, Adverse reactions to spironolactone: a report from the Boston Collaborative Drug Surveillance Program, J Am Med Assoc., 225 (1973) 40-43.13. M. Gobbini, P. Barassi, A. Cerri, S. De Munari, G. Fedrizzi, M. Santagostino, 17 alpha-O-(aminoalkyl) oxime derivatives of 3 beta, 14 beta-dihydroxy-5 beta-androstane and 3 beta-hydroxy-14-oxoseco-D-5 beta-androstane as inhibitors of Na(+), K(+)-ATPase at the digitalis receptor, J. Med. Chem., 4 (2001) 3821–3830.14. J. Templeton, V. Sashi-Kumar, D. Cote, D. Bose, D. Elliott, R. Kim, Progesterone derivatives that bind to the digitalis receptor: synthesis of 14 beta-hydroxyprogesterone: A novel steroid with positive inotropic activity, J. Med. Chem., 30 (1987) 1502–1505.15. J. Maixten, I. Bertrand, L. Lelièvre, S. Fernand, Efficacy and safety of the novel Na+, K+-ATPase inhibitor 20R 14β-amino 3β-rhamnosyl 5β-pregnan 20β-ol in a dog model of heart failure, Arzneimittelforschung., 42 (1992) 1301-1305.16. L. Figueroa, G. Ceballos, F. Díaz, A. Camacho, M. López, Biological activity of progesterone-dihydropyridimidine derivative on perfusion pressure and coronary resistance in isolated rat heart, Afr. J. Pharm. Pharmacol., 4 (2010) 170-177.17. C. Pignier, M. Keller, B. Vié, B. Vacher, M. Santelli, E. Niggli, B. Le Grand, A novel steroid‐like compound F90927 exerting positive‐inotropic effects in cardiac muscle, Br J Pharmacol., 147 (2006) 772-782.18. L. Figueroa, F. Diaz, M. Rosas, V. Mateu, E. Montano, L. Hau, M. Lopez, E. García, R. Cauich, A. Alfonso, J. Cabrera, Design and synthesis of two steroid derivatives from 2-nitroestrone and theoretical evaluation of their interaction with BRCA-1, Asian J. Green Chem., 3 (2019) 216-235.19. I.B. Obot, N. Obi, Theoretical study of benzimidazole and its derivatives and their potential activity as corrosion inhibitors, Corros. Sci., 52 (2010) 657-660.20. B. Kirchweger, J. Kratz, A. Ladurner, U. Grienke, T. Langer, V. Dirsch, J. Rollinger, In Silico Workflow for the Discovery of Natural Products Activating the G Protein-Coupled Bile Acid Receptor 1, Front Chem., 6 (2018) 242.21. K. Bayne, Revised Guide for the Care and Use of Laboratory Animals Available, Physiologist., 9 (1996) 208-211.22. L. Figueroa, F. Díaz, M. López, E. García, K. Quijano, Inotropic activity induced by carbamazepine-alkyne derivative in an isolated heart model and perfused to constant flow, BIOMEDICA., 31 (2011) 232-241.23. L. Figueroa, F. Diaz, M. Lopez, E. Garcia, K. Quijano, J. Cordoba, Changes induced by estradiol-ethylenediamine derivative on perfusion pressure and coronary resistance in isolated rat heart: L-type calcium channel, Biomed Pap., 155 (2011) 27-32.24. H. Komada, M. Okada, H. Sumitomo, Polymerization of Bicyclic Acetals. 6. Synthesis and Polymerization of (+)-(1R, 5S)-6, 8-Dioxabicyclo [3.2. 1] octane, Macromolecules., 12 (1979) 5-9.25. N. Chatterjee, P. Pandit, S. Halder, A. Patra, D. Maiti, Generation of nitrile oxides under nanometer micelles built in neutral aqueous media: Synthesis of novel glycal-based chiral synthons and optically pure 2, 8-dioxabicyclo [4.4. 0] decene core, J. Org. Chem., 7 (2008) 7775-7778.26. M. Yus, D. Ramon, One-step synthesis of substituted 6, 8-dioxabicyclo [3.2.1] octanes: easy preparation of racemic frontalin, brevicomins, and related systems, J. Org. Chem., 57 (1992) 750-751.27. O. Kataoka, S. Kitagaki, N. Watanabe, J. Kobayashi, S. Nakamura, M. Shiro, S. Hashimoto, Toward the second-generation synthesis of zaragozic acids: Construction of the 2, 8-dioxabicyclo [3.2. 1] octane core system via tandem carbonyl ylide Formation and 1, 3-dipolar cycloaddition sequence, Tetrahedron Lett., 39 (1998) 2371-2374.28. D. Wardrop, A. Velter, R. Forslund, Template-Directed C-H Insertion: Synthesis of the Dioxabicyclo [3.2. 1] octane Core of the Zaragozic Acids, Org. Lett., 3 (2001) 2261-2264.29. L. Figueroa, F. Diaz, M. Lopez, E. García, Synthesis of pregnenolone-danazol–ethylendiamine conjugate: relationship between descriptors log P, π, R m, and V m and its antibacterial activity in S. aureus and V. cholerae, Med Chem Res., 20 (2011) 847-853.30. W. Walter, W. Ruback, 2, 2, 4‐Trisubstituted 2H‐1, 3‐Oxazetes‐A New Type of Heterocycles‐A Reinvestigation. Liebigs Ann. Chem., 2 (1982) 231-239.31. K. Hourk, Frontier molecular orbital theory of cycloaddition reactions, Acc. Chem. Res., 8 (1975) 361-369.32. D. Ess, K. Houk, Theory of 1, 3-dipolar cycloadditions: distortion/interaction and frontier molecular orbital models, J. Am. Chem. Soc., 30 (2008) 10187-10198.33. Y. Prasad, P. Kumar, P. Smiles, P. Babu, QSAR studies on chalcone derivatives as antibacterial agents against Bacillus pumilis, Arkivoc., 11 (2008) 266-276.34. J. Latosińska, J. Kasprzak, Z. Kazimierczuk, Effects of chlorination and deoxiribose substitution on electron density distribution in indazole molecule studied by 35Cl NQR spectroscopy and ab initio calculations, J. Mol. Struct. THEOCHEM., 530 (2000) 217-222.35. Z. Deng, C. Chuaqui, J. Singh, Structural interaction fingerprint (SIFt): a novel method for analyzing three-dimensional protein− ligand binding interactions, J. Med. Chem., 7 (2004) 337-344.36. S. Sakkiah, S. Thangapandian, S. John, K. Lee, Pharmacophore based virtual screening, molecular docking studies to design potent heat shock protein 90 inhibitors, Eur. J. Med. Chem., 46 (2011) 2937-2947.37. L. Figueroa, F. Diaz, E. Garcia, M. Rosas, E. Pool E, Evaluation of activity of an estrogen-derivative as cardioprotector drug using an ischemia-reperfusion injury model, Int J Clin Exp Med., 8 (2015) 12041-12055.38. E. Sorkin, S. Clissold, P. Brogden, Nifedipine, Drugs., 30 (1985) 82-274.39. L. Figueroa, F. Diaz, E. García, E. Pool, M. Rosas, L. Hau, B. Sarabia, Design and synthesis of new dihydrotestosterone derivative with positive inotropic activity, Steroids., 95 (2015) 39-50.40. C. Turner, Y. Takano, I. Owan, G. Murrell, Nitric oxide inhibitor L-NAME suppresses mechanically induced bone formation in rats. Am J Physiol Endocrinol Metab., 270 (1996) E634-E639.