Barteselli Anna, Parapini Silvia, Basilico Nicoletta, Mommo Danilo, Sparatore Anna
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via C. Pascal 36, 20133 Milano, Italy.
Bioorg Med Chem. 2014 Nov 1;22(21):5757-65. doi: 10.1016/j.bmc.2014.09.040. Epub 2014 Oct 10.
With the aim to explore the potentiality of new chemical scaffolds for the design of new antimalarials, a set of new indeno[2,1-c]quinolines bearing different basic heads has been synthesized and tested in vitro against chloroquine sensitive (CQ-S) and chloroquine resistant (CQ-R) strains of Plasmodium falciparum. Most of the synthesized compounds exhibited a moderate antiplasmodial activity, inhibiting the growth of both CQ-S and CQ-R strains of P. falciparum with IC50 ranging from 0.24 to 6.9 μM and with a very low resistance index. The most potent compounds (1.2-1.3-fold the CQ on the W-2 strain) can be considered as promising 'lead compounds' to be further optimized to improve efficacy and selectivity against Plasmodia.
为了探索新型化学骨架在新型抗疟药设计中的潜力,合成了一组带有不同碱性基团的新型茚并[2,1-c]喹啉,并针对恶性疟原虫的氯喹敏感(CQ-S)和氯喹耐药(CQ-R)菌株进行了体外测试。大多数合成化合物表现出中等抗疟活性,抑制恶性疟原虫CQ-S和CQ-R菌株的生长,IC50范围为0.24至6.9μM,耐药指数非常低。最有效的化合物(对W-2菌株的活性是氯喹的1.2 - 1.3倍)可被视为有前景的“先导化合物”,有待进一步优化以提高对疟原虫的疗效和选择性。