Activity Assays of Thiadiazine Derivatives on <i>Trichomonas vaginalis </i>and Amastigote Forms of <i>Trypanosoma cruzi</i>

Abstract

Eight thiadiazine 1,1-dioxide derivatives were evaluated for antitrichomonal and antitrypanosomal activities. In vivo tests were performed on a murine model for trichomoniasis standardized in our laboratory. The capacity of compounds to clear visceral lesions in experimentally infected animals as well as their effects on the mortality time of mice were used as criteria for activity. One of the thiadiazines (compound 7b) showed an efficacy similar to that obtained with the reference drug metronidazole, although higher doses were required. Its toxicity on cell proliferation in tissue culture was moderate. In vitro assays on amastigote forms of Trypanosoma cruzi were carried out using cultures of Vero cells infected with metacyclic trypomastigotes. For one compound (1) trypanocidal activity resembled that of nifurtimox as assessed by microscopic counts of infected and uninfected cells. Unfortunately, this compound showed a high degree of cytotoxicity on Vero cell cultures.

Synthesis and Antiprotozoan Properties of New 3,5-Disubstituted-tetrahydro-2H-1,3,5-thiadiazine-2-thione Derivatives

“…On the other hand, the interaction of isothiocyanates and cysteine has been demonstrated [3]. In this context and following our interest in antiprotozoan drugs [9,10], we have synthesized 34 new tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives with the aim they could act as prodrugs able to inhibit the cysteine proteinase of some protozoan. In order to modulate the activity, three series of compounds (1, 2 and 3), in which the nature of the substituent at 3rd position changes, have been synthesized.…”

“…Three of the compounds (L-1d, D-1j and 1m) which had shown important in vitro activity against T. vaginalis were then tested in vivo. A murine model of trichomoniasis was used as previously [9]. Groups of 8 to 10 NMRI mice from Iffa Credo (Criffa, S. A., Barcelona, Spain) were used for experimental infections.…”

Actividad tripanocida y citotóxica de extractos de plantas colombianas

“…La observación del desarrollo y el conteo de los amastigotes se hizo según la metodología descrita en trabajos anteriores (16,17). Los resultados se expresaron como CE 50 , entendida como la concentración a la cual la carga de amastigotes intracelulares disminuye 50 % con respecto al control.…”

Synthesis and Antichagasic Properties of New 1,2,6-Thiadiazin-3,5-dione 1,1-Dioxides and Related Compounds

“…In previous works [1,2], we reported the antichagasic properties of 3,5-diamino-4-(5'-nitrofurfurylidene)-4H-thiadiazine 1,1-dioxide (1) and those of some 4-heteroarylidene-1,2,6-thiadiazine-3,5-dione 1,1-dioxides derived from 2a and 2e. Compounds 1 (R 1 = 5-nitro-2-furyl), 2,6-diphenethyl-4-(2-thenylidene)-1,2,6-thiadiazin-3,5-dione 1,1-dioxide and 2,6-diphenethy-4-(5'nitrofurfurylidene)-1,2,6-thiadiazin-3,5-dione 1,1-dioxide (4e) showed important in vitro antichagasic activity at 100 µg/ml.…”

“…The presence of nitro substituents in the pentaheterocyclic moiety of nifurtimox and beznidazole, as a source of free radicals, seems to be a factor which increases antichagasic activity. In this context and following our interest in antiprotozoan drugs [1,2,3], we proposed to synthesize new 4-nitroarylidene derivatives of 3,5-diamino-4H-1,2,6-thiadiazine and of 1,2,6-thiadiazin-3,5-dione 1,1 dioxides. The compounds are shown in Scheme 1.…”