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

Medicinal Chemistry Research
2011.0

Abstract

In this study, the pregnenolone–danazol–ethylendiamine conjugate (3) was synthesized and its antibacterial activity on Staphylococcus aureus and Vibrio cholerae was evaluated. In order to delineate the structural chemistry of 3 as antibacterial agent, the physicochemical descriptors log P, p, Rm, and Vm were evaluated. In this sense, the first step was achieved by reacting pregnenolone–danazol (1) with ethylendiamine and formaldehyde to form pregnenolone–danazol–ethylendiamine (3). The structure of 3 was confirmed by spectroscopy and spectrometry data. The 1 H NMR spectrum of 3 showed signals at 0.64–1.01 and 0.99–1.00 ppm corresponding to methyls presents in the steroids nucleus. In addition, several signals at 2.62–2.74 ppm for methylene bound to ester group and at 2.68–2.74 ppm for methylenes bound to amine group were found. Finally, a signal at 8.03 ppm for the proton involved in the ring of isoxazole was found. On the other hand, the results of biological activity indicate that bacterial growth of the microorganisms studied was inhibited by 3 in a manner dose-dependent. In addition, the results showed an increase in both, Rm and Vm and a decrease of log P and p values in the compound 3 in comparison with 1. These data indicate that steric impediment and degree of lipophilicity could affect the antibacterial activity of the pregnenolone–danazol–ethylendiamine conjugate.

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