Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Eur J Med Chem. 2011 Sep;46(9):4669-75. doi: 10.1016/j.ejmech.2011.05.055. Epub 2011 May 30.
A new series of 2,4,6-trisubstituted bis-pyrimidines were synthesized and evaluated for in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. Out of 16 compounds 8 compounds have shown IC(50) values in the range of 0.10-1.86 μM. Bis-pyrimidine having methyl-, methoxy-, thiomethyl- and dimehyl-phenyl substituents, exhibited higher antiamoebic activity than the reference drug metronidazole (IC(50) = 1.9 μM). The toxicological studies of active compounds on PC12-rat pheochoromocytoma cell line showed that all compounds were non-toxic at a concentration of 100 μM. 4-4'-Benzene-1,3-diylbis[6-(4-methylphenyl-2-(piperidin-1-yl)pyrimidine] (4c) was found most active (IC(50) = 0.10 μM) and least toxic among all the compounds.
合成了一系列新的 2,4,6-三取代双嘧啶，并对其进行了体外抗溶组织内阿米巴活性评估，以 HM1:IMSS 株溶组织内阿米巴为研究对象。在 16 种化合物中，有 8 种化合物的 IC50 值在 0.10-1.86 μM 范围内。具有甲基、甲氧基、硫甲基和二甲苯基取代基的双嘧啶表现出比参考药物甲硝唑（IC50 = 1.9 μM）更高的抗阿米巴活性。对活性化合物在 PC12-大鼠嗜铬细胞瘤细胞系的毒理学研究表明，所有化合物在 100 μM 浓度下均无毒性。在所有化合物中，4-4'-苯-1,3-二基双[6-(4-甲基苯基-2-(哌啶-1-基)嘧啶)]（4c）表现出最高的活性（IC50 = 0.10 μM）和最低的毒性。
