Synthesis and anti-Pneumocystis carinii pneumonia activity of novel dicationic dibenzothiophenes and orally active prodrugs
作者:Donald A. Patrick、James Edwin Hall、Brendan C. Bender、Donald R. McCurdy、W.David Wilson、Farial A. Tanious、Shankar Saha、Richard R. Tidwell
DOI:10.1016/s0223-5234(00)80027-6
日期:1999.7
synthesized and assayed for anti-PCP activity. Three of the compounds proved to be more potent and less toxic than a standard anti-PCP drug (pentamidine) when given intravenously. Unlike the carbazoles, a dibenzothiophene amidoxime prodrug given orally reduced the parasite load by more than 99%. While no quantitative correlation was seen between anti-PCP activity and DNA binding, a strong level of DNA
已经发现二阳离子咔唑对卡氏肺孢子虫肺炎(PCP)的大鼠模型具有高活性。不幸的是,即使相应的am具有高活性,被设计为前药的a胺肟衍生物也对PCP无活性。在目前的工作中,合成了一系列的2,8-和3,7-双阳离子二苯并噻吩并测定了其抗PCP活性。静脉给药时,三种化合物被证明比标准抗PCP药物(戊am)更有效且毒性更低。与咔唑不同,口服给予的二苯并噻吩a胺肟前药可将寄生虫负荷降低99%以上。虽然未发现抗PCP活性与DNA结合之间存在定量相关性,但发现强大的DNA结合水平对于抗菌活性是必需的。