title: Design and synthesis of new dihydrotestosterone derivative with positive inotropic activity.
abstract: 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.
authors.affiliation: Laboratory of Pharmaco-Chemistry, Faculty of Chemical Biological Sciences, University Autonomous of Campeche, Av. Agustín Melgar s/n, Col Buenavista C.P. 24039 Campeche Cam., Mexico. Electronic address: lauro_1999@yahoo.com.
authors.forename: Figueroa-Valverde
authors.initials: FV
authors.lastname: Lauro
authors.affiliation: Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional. Prol. Carpio y Plan de Ayala s/n Col. Santo Tomas, D.F. C.P. 11340, Mexico.
authors.forename: Díaz-Cedillo
authors.initials: DC
authors.lastname: Francisco
authors.affiliation: Laboratory of Pharmaco-Chemistry, Faculty of Chemical Biological Sciences, University Autonomous of Campeche, Av. Agustín Melgar s/n, Col Buenavista C.P. 24039 Campeche Cam., Mexico.
authors.forename: García-Cervera
authors.initials: GC
authors.lastname: Elodia
authors.affiliation: Laboratory of Pharmaco-Chemistry, Faculty of Chemical Biological Sciences, University Autonomous of Campeche, Av. Agustín Melgar s/n, Col Buenavista C.P. 24039 Campeche Cam., Mexico.
authors.forename: Pool-Gómez
authors.initials: PG
authors.lastname: Eduardo
authors.affiliation: Facultad de Nutrición, Universidad Veracruzana, Médicos y Odontologos s/n C.P. 91010, Unidad del Bosque Xalapa Veracruz, Mexico.
authors.forename: Rosas-Nexticapa
authors.initials: RN
authors.lastname: Marcela
authors.affiliation: Laboratory of Pharmaco-Chemistry, Faculty of Chemical Biological Sciences, University Autonomous of Campeche, Av. Agustín Melgar s/n, Col Buenavista C.P. 24039 Campeche Cam., Mexico.
authors.forename: Hau-Heredia
authors.initials: HH
authors.lastname: Lenin
authors.affiliation: Faculty of Medicine, University Autonomous of Campeche, Av. Patricio Trueba de Regil s/n, Col Lindavista C.P. 24090 Campeche Cam., Mexico.
authors.forename: Sarabia Alcocer
authors.initials: SA
authors.lastname: Betty
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D006352:Heart Ventricles / Q000187:drug effects; D051381:Rats; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D013196:Dihydrotestosterone
keywords: Dihydrotestosterone derivative; Inotropic activity; Metoprolol; Synthesis