Sunduru Naresh, Palne Shraddha, Chauhan Prem M S, Gupta Suman
Division of Medicinal Chemistry, Central Drug Research Institute, MG Road, Lucknow 226001, UP, India.
Eur J Med Chem. 2009 Jun;44(6):2473-81. doi: 10.1016/j.ejmech.2009.01.016. Epub 2009 Jan 27.
A series of 2,4,6-trisubstituted pyrimidines and 1,3,5-triazines have been synthesized and screened for their in vitro and in vivo antileishmanial activity against Leishmania donovani. Among all, 14 compounds have shown promising inhibition of 80-100% at 10 microg/ml against promastigotes and IC(50) in the range of 0.89-9.68 microg/ml against amastigotes. Three compounds 13, 32 and 33 with good selectivity index (S.I.) were screened for their in vivo activity in golden hamsters (Mesocricetus auratus) infected with MHOM/IN/80/Dd(8) strain of L. donovani and have shown moderate in vivo inhibition of 48-56% at a dose of 50 mg/kg x 5, i.p. route for 5 days.
已合成了一系列2,4,6-三取代嘧啶和1,3,5-三嗪，并对其针对杜氏利什曼原虫的体外和体内抗利什曼活性进行了筛选。其中，14种化合物在10微克/毫升浓度下对前鞭毛体显示出80 - 100%的有效抑制作用，对无鞭毛体的半数抑制浓度（IC50）在0.89 - 9.68微克/毫升范围内。筛选出三种具有良好选择性指数（S.I.）的化合物13、32和33，在感染杜氏利什曼原虫MHOM/IN/80/Dd(8)株的金黄仓鼠（Mesocricetus auratus）中测试其体内活性，腹腔注射途径，剂量为50毫克/千克×5天，显示出48 - 56%的中度体内抑制作用。
