Gayral P, Loiseau P M, Bories C, Brienne M J, Leclercq M, Jacques J
Faculté de Pharmacie, Université de Paris-Sud, Châtenay-Malabry, France.
Arzneimittelforschung. 1995 Oct;45(10):1122-7.
A series of 2-substituted trans-1,2-epoxyethanesulfonamides (1T), ethynesulfonamides (2), and their carboxamide analogues 3 (cis and trans) and 4 were evaluated for their antifilarial activity, first in vitro against the infective larvae of the filaria Molinema dessetae, then in vivo against the same filaria in Proechimys oris, its natural host. On the whole, compounds 2 displayed a high level of activity in vitro, while 4 showed a wider range and 3 were virtually inactive. The modest activity found within the series 1T was assumed to be due, in part, to the instability of the products under the conditions of the biological tests. Five new compounds within the series 1T, 2 and 4 showed a macrofilaricidal activity in vivo. There is no clear correlation between in vivo and in vitro data. It was observed, however, that within the series 2 and 4 all the compounds active in vivo were among the most potent compounds in vitro. Nevertheless, the in vitro model, although of limited value, could help in selecting compounds for further evaluation within a given series.
对一系列2-取代的反式-1,2-环氧乙烷磺酰胺（1T）、乙炔磺酰胺（2）及其羧酰胺类似物3（顺式和反式）和4进行了抗丝虫活性评估，首先在体外针对丝虫莫利内马·德塞塔的感染性幼虫进行评估，然后在体内针对其天然宿主奥氏原鼠体内的同一种丝虫进行评估。总体而言，化合物2在体外表现出高水平的活性，而4显示出更广泛的活性范围，3实际上无活性。1T系列中发现的适度活性部分归因于产物在生物学测试条件下的不稳定性。1T、2和4系列中的五种新化合物在体内表现出杀成虫活性。体内和体外数据之间没有明显的相关性。然而，观察到在2和4系列中，所有在体内有活性的化合物都是体外最有效的化合物之一。尽管体外模型价值有限，但它有助于在给定系列中选择化合物进行进一步评估。
