A nitroimidazole-thiadiazole derivative with curative action in experimentalTrypanosoma cruziinfections

Topical chemotherapy for experimental African trypanosomiasis with cerebral involvement: the use of melarsoprol combined with the 5‐nitroimidazole, megazol

“…A further active 5-nitroimidazole compound (megazol) has been developed (Asto & Berkelhammer 1986) which shows activity against Trypanosoma cruzi cultures (Filardi & Brener 1982;Lages-Silva et al 19yo) and has also been used, in combination with suramin, to cure T. brucei infections in mice and sheep (Bouteille et al 1994;. This paper examines the use of rnegazoUdimethy1-sulphoxide gel given topically together with melarsoprol/propylene glycol gel.…”

Novel Therapeutic Strategies for Chagas` Disease

“…Few synthetic compounds have the same remarkable curative effects for the treatment of Chagas disease as megazol [2-amine-5-(1-methyl-5-nitro-2-imidazol-2-yl) 1,3,4 thiadiazole] (4) (Berkelhammer & Asato, 1968), a 1,3,4-thiadiazole nitroimidazole derivative that in experiments with mice infected with Colombian and  T. cruzi strains showed higher rates of cure compared to the standard treatment using nitrofurazone (1), nifurtimox (2) and benznidazole (3) ( Table 1) (Filardi & Brener, 1982 All derivatives tested by Chauvière and colleagues (2003) produced a decrease in trypanocidal activity; however the molecular architecture of the prototype megazol (4) is the one that presents the best bioactivity profile against T. brucei, T. cruzi, L. infantum and L. donovani, without cytotoxicity to macrophage cells. Little is known about the metabolism of megazol, and despite its nitro-heterocyclic nature, some authors disagree on the metabolic reduction of the nitro group by nitroreductases as being critical for its trypanocidal activity.…”

Article Synthesis and Trypanocidal Activity of Novel 2,4,5-Triaryl-N-Hydroxylimidazole Derivatives

“…All new 2,4,5-triaryl-N-hydroxyimidazole derivatives 3-12 were purified by recrystallization from a 9:1 solution of ethanol/water. (6). Yellow solid; mp 218-219 °C; yield 69%; …”

“…Megazol [1-methyl-2-(5-amino-1,3,4-thiadiazole)-5-nitroimidazole] is a nitroheterocyclic derivative shown to be highly active against T. cruzi in vitro and in vivo, including strains that are resistant to benznidazole [5][6][7]; thus, it has become a core structure for the design of new drugs for the treatment of Chagas disease. Megazol has been described as a scavenger of trypanothione, the cofactor for trypanothione reductase [8,9].…”