Synthesis and Antibacterial Activity of Pregnenolone- Carbamazepine Conjugate on Proteus mirabilis

Abstract

In this work, the steroid-carbamazepine conjugate was synthesized. The route involve preparation of carbamazepine-aminocaproic acid compound (3) followed by coupling of hemisuccinate-pregnenolone (4) to the 3 compound and formation of pregnenolone-carbamazepine conjugate (5). In addition, the evaluation of antimicrobial effect of the different compounds on Proteus mirabilis was made by the method of microbial minimal inhibitory (MIC). The structure from 5 was confirmed by spectroscopy and spectrometry data. The ¹H NMR spectrum showed, up field shifts at 0.60 and 0.98 ppm for methyls substituents in the steroid nucleus. In addition, other signals display chemical shifts at 1.40-1.60 and 1.80-2.07 ppm for methylens present in the steroid nucleus. In addition, at down field there is a signal at 6.8 ppm for the proton involved in central seven-membered azepine and two chemical shifts at 7.7 and 7.9 ppm corresponding to protons in the benzene rings. Finally, a signal at 9.02 ppm for functional amide groups involved in the spacer arm between the steroid nucleus and carbamazepine. Other results showed that bacterial growth of Proteus mirabilis was inhibited with cefotaxime (MIC = 5.23 × 10^-4 mmol), gentamicin (MIC = 2.68 × 10^-5 mmol), ciprofloxacin (3.01 × 10^-3) and pregnenolone-carbamazepine conjugate (MIC = 3.18 × 10^-4 mmol). All this data indicate that pregnenolone-carbamazepine conjugate had different antibacterial potency in comparison with cefotaxime (b-lactam antibiotic), gentamycin (inhibitor of synthesis of protein) and ciprofloxacin (inhibitor of DNA gyrase). In order to develop new strategies to synthesize the pregnenolone-carbamazepine conjugate, that could be used as antibiotic- drugs on Proteus mirabilis bacteria.