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

Authors : Figueroa Lauro, Lopez Maria, Diaz Francisco, Rosas Marcela, Mateu Virginia, Garcimarrero Alejandra, Borges Yaritza

Pages : 1-12

Doi:10.15671/hjbc.602029

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Publication Date : 2020-04-17

Article Type : Research

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