Design and synthesis of new dihydrotestosterone derivative with positive inotropic activity

Figueroa Valverde Lauro, Díaz Cedillo Francisco, García Cervera Elodia, Pool Gómez Eduardo, Rosas Nexticapa Marcela, Hau Heredia Lenin, Sarabia Alcocer Betty

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

© 2015 Elsevier Inc. There are several reports which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action of steroid derivatives at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, two dihydrotestosterone derivatives (compounds 5 and 10) were synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. In the first stage, the Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of the steroid derivatives. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the compound 5 was evaluated by measuring left ventricular pressure in absence or presence of following compounds; nifedipine, flutamide, indomethacin, prazosin, isoproterenol, propranolol and metoprolol. The results showed that the compound 5 significantly increased the perfusion pressure and coronary resistance in comparison with dihydrotestosterone, compound 10 and the control conditions. Other data indicate that 5 increase left ventricular pressure in a dose-dependent manner (0.001-100 nM); nevertheless, this phenomenon was significantly inhibited only by propranolol or metoprolol at a dose of 1 nM. These data suggest that positive inotropic activity induced by the compound 5 is through β1-adrenergic receptor however, this effect was independent of cAMP levels. This phenomenon is a particularly interesting because the positive inotropic activity induced by this steroid derivative involves a molecular mechanism different in comparison with other positive inotropic drugs.
Original languageAmerican English
Pages (from-to)39-50
Number of pages33
JournalSteroids
DOIs
StatePublished - 1 Jan 2015

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Dihydrotestosterone
Ventricular Pressure
Steroids
Derivatives
Metoprolol
Propranolol
Perfusion
Flutamide
Pressure
Prazosin
Nifedipine
Isoproterenol
Indomethacin
Adrenergic Receptors
Bioactivity
Rats
Pharmaceutical Preparations

Cite this

Lauro, F. V., Francisco, D. C., Elodia, G. C., Eduardo, P. G., Marcela, R. N., Lenin, H. H., & Betty, S. A. (2015). Design and synthesis of new dihydrotestosterone derivative with positive inotropic activity. Steroids, 39-50. https://doi.org/10.1016/j.steroids.2014.12.026
Lauro, Figueroa Valverde ; Francisco, Díaz Cedillo ; Elodia, García Cervera ; Eduardo, Pool Gómez ; Marcela, Rosas Nexticapa ; Lenin, Hau Heredia ; Betty, Sarabia Alcocer. / Design and synthesis of new dihydrotestosterone derivative with positive inotropic activity. In: Steroids. 2015 ; pp. 39-50.
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Design and synthesis of new dihydrotestosterone derivative with positive inotropic activity. / Lauro, Figueroa Valverde; Francisco, Díaz Cedillo; Elodia, García Cervera; Eduardo, Pool Gómez; Marcela, Rosas Nexticapa; Lenin, Hau Heredia; Betty, Sarabia Alcocer.

In: Steroids, 01.01.2015, p. 39-50.

Research output: Contribution to journalArticle

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AU - Lauro, Figueroa Valverde

AU - Francisco, Díaz Cedillo

AU - Elodia, García Cervera

AU - Eduardo, Pool Gómez

AU - Marcela, Rosas Nexticapa

AU - Lenin, Hau Heredia

AU - Betty, Sarabia Alcocer

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N2 - © 2015 Elsevier Inc. There are several reports which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action of steroid derivatives at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, two dihydrotestosterone derivatives (compounds 5 and 10) were synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. In the first stage, the Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of the steroid derivatives. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the compound 5 was evaluated by measuring left ventricular pressure in absence or presence of following compounds; nifedipine, flutamide, indomethacin, prazosin, isoproterenol, propranolol and metoprolol. The results showed that the compound 5 significantly increased the perfusion pressure and coronary resistance in comparison with dihydrotestosterone, compound 10 and the control conditions. Other data indicate that 5 increase left ventricular pressure in a dose-dependent manner (0.001-100 nM); nevertheless, this phenomenon was significantly inhibited only by propranolol or metoprolol at a dose of 1 nM. These data suggest that positive inotropic activity induced by the compound 5 is through β1-adrenergic receptor however, this effect was independent of cAMP levels. This phenomenon is a particularly interesting because the positive inotropic activity induced by this steroid derivative involves a molecular mechanism different in comparison with other positive inotropic drugs.

AB - © 2015 Elsevier Inc. There are several reports which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action of steroid derivatives at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, two dihydrotestosterone derivatives (compounds 5 and 10) were synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. In the first stage, the Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of the steroid derivatives. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the compound 5 was evaluated by measuring left ventricular pressure in absence or presence of following compounds; nifedipine, flutamide, indomethacin, prazosin, isoproterenol, propranolol and metoprolol. The results showed that the compound 5 significantly increased the perfusion pressure and coronary resistance in comparison with dihydrotestosterone, compound 10 and the control conditions. Other data indicate that 5 increase left ventricular pressure in a dose-dependent manner (0.001-100 nM); nevertheless, this phenomenon was significantly inhibited only by propranolol or metoprolol at a dose of 1 nM. These data suggest that positive inotropic activity induced by the compound 5 is through β1-adrenergic receptor however, this effect was independent of cAMP levels. This phenomenon is a particularly interesting because the positive inotropic activity induced by this steroid derivative involves a molecular mechanism different in comparison with other positive inotropic drugs.

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