Cretton Sylvian, Bartholomeusz Trixie A, Mehl Florence, Allenbach Yves, Matheeussen An, Cos Paul, Maes Louis, Christen Philippe
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest- Ansermet 30, CH-1211 Geneva 4, Switzerland.
Med Chem. 2014;10(8):753-8. doi: 10.2174/1573406410666140507095430.
A series of twelve analogs carrying fluoro, chloro, bromo and iodo halogens on the ortho, meta and para positions of a benzoyloxytropane skeleton were synthesized by a simple acylation of 8-methyl-8-aza-bicyclo[3.2.1]octan- 3α-ol by halogenobenzoyl chlorides. The compounds were evaluated in vitro against Plasmodium falciparum (P. f.), Trypanosoma brucei brucei (T. b. b.), Trypanosoma cruzi (T. c.) and Leishmania infantum (L. i.). This study shows that the presence of a halogenated atom and its position on the aromatic ring are important for in vitro activity. Compounds 4 (IC50 = 3.6 µM), 8 (IC50 = 6.7 µM), 5 (IC50 = 8.1 µM) and 7 (IC50 = 9.5 µM) were found the most active against P. f., whereas compounds 12 (IC50 = 5.1 µM), 11 (IC50 = 5.6 µM) and 9 (IC50 = 5.8 µM) exhibited the most pronounced activity against T. b. b. This series of compounds can be considered as non-toxic to the human cell line MRC-5.
通过卤代苯甲酰氯对8-甲基-8-氮杂双环[3.2.1]辛烷-3α-醇进行简单的酰化反应，合成了一系列在苯甲酰氧基托烷骨架的邻位、间位和对位带有氟、氯、溴和碘卤素的十二个类似物。对这些化合物进行了体外抗恶性疟原虫（P. f.）、布氏锥虫（T. b. b.）、克氏锥虫（T. c.）和婴儿利什曼原虫（L. i.）的活性评估。该研究表明，卤原子的存在及其在芳环上的位置对体外活性很重要。发现化合物4（IC50 = 3.6 µM）、8（IC50 = 6.7 µM）、5（IC50 = 8.1 µM）和7（IC50 = 9.5 µM）对恶性疟原虫的活性最高，而化合物12（IC50 = 5.1 µM）、11（IC50 = 5.6 µM）和9（IC50 = 5.8 µM）对布氏锥虫表现出最显著的活性。这一系列化合物对人细胞系MRC-5可认为是无毒的。
