In Vitro and In Silico Analysis of New n-Butyl and Isobutyl Quinoxaline-7-carboxylate 1,4-di-N-oxide Derivatives against Trypanosoma cruzi as Trypanothione Reductase Inhibitors.

American trypanosomiasis is a worldwide health problem that requires attention due to ineffective treatment options. We evaluated n-butyl and isobutyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives against trypomastigotes of the Trypanosoma cruzi strains NINOA and INC-5. An in silico analysis of the interactions of 1,4-di-N-oxide on the active site of trypanothione reductase (TR) and an enzyme inhibition study was carried out. The n-butyl series compound identified as T-150 had the best trypanocidal activity against T. cruzi trypomastigotes, with a 13% TR inhibition at 44 µM. The derivative T-147 behaved as a mixed inhibitor with Ki and Ki' inhibition constants of 11.4 and 60.8 µM, respectively. This finding is comparable to the TR inhibitor mepacrine (Ki = 19 µM).

Evaluation of the anti-diarrheal activity of Salvia connivens.

CONTEXT: Diarrheal disease is a leading cause of mortality and morbidity and accounts for 5-8 million deaths worldwide each year. Salvia connivens Epling (Lamiaceae) is used to treat sore throat, fevers, diarrhea, malaria, and also is used as an antipyretic. OBJECTIVE: The present study evaluates the efficacy of S. connivens in the treatment of diarrhea using animal models. MATERIALS AND METHODS: The anti-diarrheal effect of methanol extract of S. connivens was investigated on mice with castor oil, arachidonic acid (AA) or prostaglandin E2 (PGE2)-induced diarrhea. On Wistar rats, the activity was evaluated on the intestinal transit and Castor oil-induced enteropooling. RESULTS: The methanol extract at doses of 6.25, 12.5, 25, 50, 100, and 200 mg/kg on castor oil-induced diarrhea reduced the diarrhea by 32.3, 41.9, 67.7, 74.2, 83.3, and 100%, respectively. Additionally, this extract, at doses of 200 mg/kg, inhibited AA-induced diarrhea by 100%. The methanol extract produced no effect on PGE2-induced diarrhea at the same doses. In Wistar rats, at dose of 200 mg/kg, the methanol extract inhibited intestinal transit and decreased the volume of intestinal secretion induced by castor oil. DISCUSSION: The methanol extract showed anti-diarrheal effect on the animal models used. Phytochemical screening revealed the presence of alkaloids, tannins, and saponins which may be responsible for this effect. The extract did not cause any mortality or any visible signs of toxicity or differences in food and water uptake were seen. CONCLUSIONS: These results justify the use of S. connivens as an anti-diarrheal agent.