Current Therapeutics, Their Problems, and Sulfur-Containing-Amino-Acid Metabolism as a Novel Target against Infections by “Amitochondriate” Protozoan Parasites

Abstract

SUMMARY The “amitochondriate” protozoan parasites of humans Entamoeba histolytica, Giardia intestinalis, and Trichomonas vaginalis share many biochemical features, e.g., energy and amino acid metabolism, a spectrum of drugs for their treatment, and the occurrence of drug resistance. These parasites possess metabolic pathways that are divergent from those of their mammalian hosts and are often considered to be good targets for drug development. Sulfur-containing-amino-acid metabolism represents one such divergent metabolic pathway, namely, the cysteine biosynthetic pathway and methionine γ-lyase-mediated catabolism of sulfur-containing amino acids, which are present in T. vaginalis and E. histolytica but absent in G. intestinalis. These pathways are potentially exploitable for development of drugs against amoebiasis and trichomoniasis. For instance, l-trifluoromethionine, which is catalyzed by methionine γ-lyase and produces a toxic product, is effective against T. vaginalis and E. histolytica parasites in vitro and in vivo and may represent a good lead compound. In this review, we summarize the biology of these microaerophilic parasites, their clinical manifestation and epidemiology of disease, chemotherapeutics, the modes of action of representative drugs, and problems related to these drugs, including drug resistance. We further discuss our approach to exploit unique sulfur-containing-amino-acid metabolism, focusing on development of drugs against E. histolytica.

Amebiasis: aspectos clínicos, terapéuticos y de diagnóstico de la infección

“…Sin embargo, este fármaco tiene efectos tóxicos 39,42 y se han reportado fracasos en el tratamiento de algunas bacterias y protozoos 43,44 , pero no se han observado aislados de E. histolytica resistentes al fármaco 45 . Por estas razones se hace necesaria la búsqueda de nuevos fármacos amebicidas.…”

Isolation and antitrichomonal activity of the chemical constituents of the leaves of Maytenus phyllanthoides Benth. (Celastraceae)

“…Fraction A was purified by TLC using CH 2 Cl 2 -acetone (98:2) as eluent to give 80 mg of veratric acid (2). From fraction B, after column chromatography on silica gel 60 (37-74 mm) eluted with mixtures of CH 2 Cl 2 -EtOAc, 30 mg of vanillic acid (3) were obtained.…”

“…Chromatography of fraction G over Sephadex LH-20 afforded 36 fractions that, after a TLC analysis, were combined in eight fractions (1)(2)(3)(4)(5)(6)(7)(8). Fraction G8 chromatographed on silica gel 60 (37-74 mm) eluted with a mixture of hexane-ethyl acetate of increasing polarity.…”

“…Fifty-six fractions were obtained and combined into 10 fractions. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Lupeol (6 mg) and oleanolic acid (3 mg) were obtained from fraction G8g7 after purification by TLC where they eluted with CHCl 3 -EtOAc (98:2).…”

“…1 Trichomonas vaginalis is a flagellated protist that causes trichomoniasis, a common sexually transmitted human infection, increasingly recognized as an important disease in both women and men. 2 According to the WHO, approximately 180 million cases are reported annually worldwide. 3 Studies indicate that trichomoniasis is associated with the predisposition to cervical cancer, pelvic inflammatory disease, infertility, increasing infections by human papillomavirus (HPV), birth outcomes, and human immunodeficiency virus (HIV).…”