nifurtimox and Leishmaniasis

Topics: Allopurinol; Aminoquinolines; Antimony; Antimony Sodium Gluconate; Cryosurgery; Humans; Leishmaniasis; Leishmaniasis, Mucocutaneous; Levamisole; Liposomes; Meglumine; Meglumine Antimoniate; Metronidazole; Nifurtimox; Organometallic Compounds; Phenothiazines; Rifampin

Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Two very common neglected tropical diseases are Chagas' disease and leishmaniasis. Chagas' disease is a severe health problem, mainly in Latin America, causing approximately 50000 deaths a year and millions of people are infected. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. On the other hand, Leishmaniasis represents complex diseases with an important clinical and epidemiological diversity. It is endemic in 88 countries 72 of which are developing countries and it has been estimated that are 12 million people infected and 350 million are in areas with infection risk. On this basis, research on organic compounds that can be used against these two diseases is an important target. A very simple, green, and efficient protocol is developed in which bismuth nitrate pentahydrate is employed as a Lewis acid catalyst in aqueous media under microwave irradiation for the synthesis of various 2-aryl substituted benzimidazoles from aldehydes and o-phenylenediamine. Other salient features of this protocol include milder conditions, atom-economy, easy extraction, and no wastes. Nine 1H-benzimidazole derivatives (1-9) with substituents at positions 2 and 5 were synthesized and the structure of the compounds was elucidated by spectroscopic methods. The compounds were screened to identify whether they posses pharmacological activity against Chagas' disease and leishmaniasis. Compound 8 showed better activity than the control Nifurtimox against INC-5 Trypanosoma cruzi strain whereas compounds 3 and 9 have demonstrated potent leshmanicidal activity. A systematic green synthetic procedure and in vitro biological evaluation of nine 1H-benzimidazoles are described.

Topics: Amphotericin B; Antiprotozoal Agents; Benzimidazoles; Chagas Disease; Green Chemistry Technology; Heating; Leishmania mexicana; Leishmaniasis; Microwaves; Nifurtimox; Nitroimidazoles; Trypanosoma cruzi

Exploring the influence of different substitution patterns of 2H-benzimidazole 1,3-dioxide derivatives (BzNO) we prepared fifteen new derivatives. Initially the BzNO were tested against Trypanosoma cruzi Tulahuen 2 strain epimastigote form rendering very potent anti-T. cruzi agents. Moreover, the BzNO were able to inhibit the growth of virulent and resistant to Benznidazole strains (CL Brener clone, Colombiana, and Y strains) and to Leishmania braziliensis. Interestingly, BzNO exhibited very high selectivity index and particularly the spiro-BzNO 13 provokes an important diminution of amastigotes in Vero cells. Besides, it was found a diminution of acetate and glycine as excreted metabolites but without increase of parasite glucose uptake indicating that the glycosome is probably not involucrate in the 2H-benzimidazole 1,3-dioxides mechanism of action.

Topics: Animals; Benzimidazoles; Cell Line; Cell Survival; Chagas Disease; Glucose; Leishmania braziliensis; Leishmaniasis; Macrophages; Mice; Mitochondria; Oxidoreductases; Trypanocidal Agents; Trypanosoma cruzi

Topics: Antimony; Drug Administration Schedule; Humans; Leishmaniasis; Meglumine; Meglumine Antimoniate; Nifurtimox; Nitrofurans; Organometallic Compounds

Topics: Animals; Antiprotozoal Agents; Chlorpromazine; Clofazimine; Electron Transport; Leishmania donovani; Leishmania mexicana; Leishmaniasis; Leishmaniasis, Visceral; Methylene Blue; Methylphenazonium Methosulfate; Mice; Mice, Inbred BALB C; Naphthoquinones; Nifurtimox; Vitamin K

At a dosage level of 8 to 10 mg/kg body-weight daily for 120 days nifurtimox was associated with clinical healing of cutaneous leishmaniasis in five of eight patients. At a dosage level of 20 mg/kg body-weight daily for 10 days in six of 10 patients the skin ulcer healed. Results and the reasons why both schemes are impracticable are briefly discussed.

Topics: Adolescent; Adult; Aged; Child; Drug Administration Schedule; Female; Humans; Leishmaniasis; Leishmaniasis, Mucocutaneous; Male; Middle Aged; Nifurtimox; Nitrofurans

A novel 8-aminoquinolone compound, 8(6-4' 3-hydroxybutyl)piperazin-1'-ylhexylamino)-6-methoxyquinoline di(hydrogen maleate), moxipraquine, 349C59, was shown to be active against experimental infections with Trypanosoma cruzi. It was effective in suppressing parasitaemia but did not eradicate the infection from mice or guinea-pigs. Other clinically tested drugs, including nifurtimox, were likewise incapable of eradicating the parasite from infected mice. Moxipraquine was less potent against mouse infections with strain Peru than it was against other strains of T. cruzi. In limited tests, moxipraquine was effective on experimental infections of Leishmania major, L. mexicana mexicana and L. brasiliensis panamensis but not L.b. brasiliensis. Significant foetal toxicity, observed experimentally in rats and rabbits, resulted in the termination of clinical trials.

Topics: Aminoquinolines; Animals; Chagas Disease; Culture Techniques; Female; Fetus; Furazolidone; Guinea Pigs; Leishmaniasis; Lethal Dose 50; Maternal-Fetal Exchange; Mice; Nifurtimox; Nitrofurazone; Pregnancy; Primaquine; Rabbits; Rats; Time Factors