Synthesis and Antibacterial Activity of Pregnenolone–Vitamin B1 Conjugate
Lauro Figueroa Valverde,1* Francisco Díaz Cedillo,3 Guillermo Ceballos Reyes,2 María López Ramos1
1 Universidad Autónoma de Campeche, Av. Agustín Melgar, Col Buenavista, 24030 Campeche, Campeche, México. Phone: (981) 8119800 Ext. 73006. Fax: (981) 8119800 Ext. 73002. *Responsible author: lauro_1999@yahoo.com.
2 Escuela de Medicina del Instituto Politécnico Nacional. Plan de San Luís y Díaz Mirón, Col. Santo Tomás, 11340, D.F., México.
3 Escuela de Ciencias Biológicas del Instituto Politécnico Nacional. Prolongación Carpio y Plan de Ayala, Col. Santo Tomás, 11340, D.F., México.
]]> Recibido el 7 de febrero de 2008
Abstract
In this work was synthesized a pregnenolone derivative; the route involved preparation of pregnenolone hemisuccinate (2) by esterification of pregnenolone (1) with succinic anhydride followed by formation of the hemisuccinate of pregnenolone–vitamin B1 conjugate (3). The antibacterial activity of compound 3, as well as 2 and vitamin B1, was evaluated in vitro on S. aureus, K. pneumoniae and E. coli using dilution method and the minimum inhibitory concentration (MIC). The structure of 3 was confirmed by spectroscopy and spectrometry data. The 1H NMR spectrum showed, up field shifts at 2.52 and 2.58 ppm for methyls present in the heterocyles rings; at 2.90 and 3.77 methylenes of the hydroxietilen moiety bonded to thiazol ring, in addition the hydrogens of the methylene between the pyrimidine and thiazol ring appears at 4.39 ppm. At down field there are two chemical shifts (7.54, 8.33) corresponding to protons in the heterocyles. The results of the biological activity indicate that the bacterial growth of the microorganisms studied was inhibited by 3, and 2 in a manner dose–dependent, but not by vitamin B1. These data suggest that quaternary amine group involved in the HPVB1 conjugate requires the hydrophobic region of the steroid in order to interact with some components of bacterial cell, disturbing the bacterial growth and to cause cell death.
Key words: Pregnenolone, Hemisuccinate–pregnenolone–vitamine B1, Quaternary amine.
Resumen
En este trabajo fue sintetizado un derivado de pregnenolona, la ruta involucra la preparación de hemisuccinato de pregnenolona (2) por esterificación de pregnenolona (1) con anhídrido succínico, seguido por formación del conjugado hemisuccinato de pregnenolona–vitamina B1 (3). La actividad antibacterial del compuesto 3, así como la de 2 y de la vitamina B1 fue evaluada en vitro sobre S. aureus, K. pneumoniae and E. coli usando el método de dilución y la concentración mínima inhibitoria (CMI). La estructura 3 fue confirmada por datos espectroscópicos y espectrométricos. El espectro de 1H NMR mostró cambios a 2.52 y 2.58 ppm para metilos presentes en los anillos heterocíclicos; a 2.90 y 3.77 para metilenos del hidroxietilén enlazado al anillo de tiazol; además, los hidrógenos del metileno entre la piridina y el anillo de tiazol aparecen a 4.39 ppm. A campos bajos hay dos cambios químicos (7.54, 8.33) correspondientes a protones en los heterociclicos. Los resultados de la actividad biológica indican que el crecimiento bacterial de los microorganismos estudiados fue inhibido por 3 y 2 en una manera dosis–dependiente pero no por la vitamina B1 . Esos datos sugieren que el grupo amino cuaternario envuelto en el conjugado hemisuccinato de pregnenolona–vitamina B1 posiblemente requiere la región hidrófobica del esteroide para interactuar con algunos componentes de la célula bacterial perturbando el crecimiento bacterial y causar muerte celular.
Palabras clave: Pregnenolona, Hemisuccinato–pregnenolona–vitamina B1, Quaternary amine.
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Acknowledgements
Lauro Figueroa Valverde is grateful to Dr. Beauregard Cruz Juan Jose and Maria–Figuer.
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