Department of Medicinal Chemistry, School of Pharmacy, Shaheed-Beheshti University of Medical Sciences, Tehran, Iran.
Chem Biol Drug Des. 2012 Mar;79(3):326-31. doi: 10.1111/j.1747-0285.2011.01278.x. Epub 2012 Jan 11.
Novel aminoquinoline β-aminoalcohol and oxazolidinone derivatives were designed, synthesized, and evaluated for in vitro antiplasmodial activity against a chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. A few β-aminoalcohol derivatives were more potent than chloroquine against chloroquine-sensetive Plasmodiums. The potency of these derivatives decreased against chloroquine-resistant species in all cases (higher resistance indices), suggesting a possible cross-resistance between this group of compounds and chloroquine which could be due to their structural similarity. Although changing β-aminoalcohols to their oxazolidinone counterparts decreased the potency in all the cases, the compounds were still active and the resistance indices for these compounds improved significantly in comparison with those of β-aminoalcohols. This may indicate the absence of cross-resistance between these new derivatives and chloroquine.
新型氨基喹啉β-氨基醇和恶唑烷酮衍生物被设计、合成，并评估了它们对体外抗疟原虫活性，针对的是氯喹敏感（3D7）和氯喹耐药（K1）的恶性疟原虫。一些β-氨基醇衍生物对氯喹敏感的恶性疟原虫比氯喹更有效。在所有情况下，这些衍生物对氯喹耐药的物种的效力都降低了（更高的耐药指数），这表明这一组化合物与氯喹之间可能存在交叉耐药性，这可能是由于它们的结构相似性。虽然将β-氨基醇换成恶唑烷酮类似物在所有情况下都降低了活性，但这些化合物仍然具有活性，与β-氨基醇相比，这些化合物的耐药指数有了显著改善。这可能表明这些新衍生物与氯喹之间不存在交叉耐药性。
