Résumé
Toxoplasma gondii infection is widespread worldwide, not only posing a serious threat to human food safety and animal husbandry, but also endangering human health. The selectivity index was employed to measure anti-T. gondii activity. Hederagenin (HE) exhibited potent anti-T. gondii activity and low cytotoxicity. For this reason, HE was selected for in vivo experiments. HE showed 64.8%±13.1% inhibition for peritoneal tachyzoites in mice, higher than spiramycin 56.8%±6.0%. Biochemical parameters such as alanine aminotransferase, aspartate aminotransferase, glutathione, and malondialdehyde, illustrated that HE was a good inhibitor of T. gondii in vivo. This compound was also effective in relieving T. gondii-induced liver damage. Collectively, it was demonstrated that HE had potential as an anti-T. gondii agent.
Résumé
Toxoplasma gondii infection is widespread worldwide, not only posing a serious threat to human food safety and animal husbandry, but also endangering human health. The selectivity index was employed to measure anti-T. gondii activity. Hederagenin (HE) exhibited potent anti-T. gondii activity and low cytotoxicity. For this reason, HE was selected for in vivo experiments. HE showed 64.8%±13.1% inhibition for peritoneal tachyzoites in mice, higher than spiramycin 56.8%±6.0%. Biochemical parameters such as alanine aminotransferase, aspartate aminotransferase, glutathione, and malondialdehyde, illustrated that HE was a good inhibitor of T. gondii in vivo. This compound was also effective in relieving T. gondii-induced liver damage. Collectively, it was demonstrated that HE had potential as an anti-T. gondii agent.
Résumé
Epilepsy is the most frequent nearological affiction and afflicts 1% about of the worlds population. Currently there is an urgent need for the development of novel anticonvulsants with higher levels of potency and lower levels of toxicity. In this paper, a series of new 6-[substituted-phenyT] thiazolo[3,2-b][1.2.4]triazole derivatives were synthesized and tested for their anticonvulsant activities using the maximal electroshock [MES] and subcutaneous pentylenetetrazole [PTZ] screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. In these compounds, 6-[4-fluorophenyl] thiazolo[3,2-b][l,2,4]triazole [3c] showed selective protection against the MES seizures with an ED[50] value of 49.1 mg/Kg and a TD[50] value of 94.1 mg/Kg, which provided compound 3c a protective index [PI = TD[50]/ED[50] of 1.9 in the MES test. 6-[4-Propoxyphenyl]thiazolo[3,2-b][l,2,4]triazole [5b] was found to be active in both models, i.e. MES test and PTZ test. In the PTZ screen, compound 5b gave an ED[50] of 63.4 mg/Kg and a TD[50] of 105.6 mg/Kg, resulting in a PI value of 1.7 which is higher than carbamazepine
Résumé
Considerable interest has been focused on the triazole structure, which has been known to possess a broad spectrum of biological activities such as antitumor, anti-inflammatory, antimicrobial, antiviral, and anticonvulsant activities. Before this, several heterocyclic compounds containing triazole were synthesized that had shown considerable anticonvulsant activity. As part of our continuous research in this area, we have synthesized several new 7-substituted-5-phenyl-[1, 2, 4] triazolo[l, 5-#] pyrimidines [compounds 3a-3i, 5a-5micro] through incorporating triazole moiety into the pyrimidine ring, which are expected to have the synergistic effect in dealing with the epilepsy. Their anticonvulsant activities were measured through the Maximal electroshock [MES] test. Carbamazepine and valproate were considered as positive control drugs with anticonvulsant effects [ED[50] = 11.8 and 272 mg/Kg]. Amongst the compounds tested, compound 3f, 7-[heptyloxy]-5-phenyl-[l, 2, 4] triazolo[l, 5-a] pyrimidine, showed potent anticonvulsant activity with ED[50] 84.9 mg/Kg, which was weaker than carbamazepine, but better than valproate