Synthesis, Characterization and Antibacterial Activity of Danazol-Pregnenolone Conjugate

Abstract

This work reports the synthesis of the danazol-pregnenolone conjugate (5). The route involved preparation of danazol succinate (3) by esterification of danazol (1) with succinic anhydride (2) followed by the reaction of 3 with pregnenolone (4) for synthesis of 5. Additionally, another route used in this work for synthesis of 5, was made by means of the reaction between pregnenolone-succcinate (6) and danazol to form 5. The antibacterial activity of compound 3, as well as 5 and 6, was evaluated in vitro on S. aureus, K. pneumoniae and E. coli using dilution method and the minimum inhibitory concentration (MIC). The structure of 5 was confirmed by spectroscopy and spectrometry data. The ¹H NMR spectrum showed, up field shifts at 0.64, 0.85, 1.02 and 1.03 ppm for methyls present in the heterocyles rings at 1.87 ppm for proton present in alkyne (C≡CH). In addition, a signal at 2.62 ppm was found for methylene involved in arm spacer between the fragments of danazol and pregnenolone. Another chemical shifts at 5.39 and 7.89 ppm were exhibited for the protons involved in azole-ring. Finally, the presence of the danazol-pregnenolone conjugate was further confirmed from mass spectrum which showed a molecular ion at m/z 797.94. The results of the biological activity indicate that the bacterial growth of the microorganisms studied was inhibited by 3, 5 and 6 in a manner dosedependent. In conclusion, experimental data suggest that quaternary amine group involved in the danazol-pregnenolone conjugate require only the hydrophobic region of pregnenolone, in order to interact with the cell surface and perturb bacterial growth of S. aureus, E. coli and K. pneumoniae.