Ansari Mohammad Fawad, Hayat Faisal, Inam Afreen, Kathrada Fatima, van Zyl Robyn L, Coetzee Maureen, Ahmad Kamal, Shin Dongyun, Azam Amir
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 406-799, South Korea.
Bioorg Med Chem Lett. 2017 Feb 1;27(3):460-465. doi: 10.1016/j.bmcl.2016.12.043. Epub 2016 Dec 18.
In an endeavor to develop efficacious antiprotozoal agents 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives (5-14) were synthesized, characterized and biologically evaluated for antiprotozoal activity. The compounds were screened in vitro against the HM1: IMSS strain of Entamoeba histolytica and NF54 chloroquine-sensitive strain of Plasmodium falciparum. Among the synthesized compounds six exhibited promising antiamoebic activity with IC values (0.14-1.26μM) lower than the standard drug metronidazole (IC 1.80μM). All nine compounds exhibited antimalarial activity (IC range: 1.42-19.62μM), while maintaining a favorable safety profile to host red blood cells. All the compounds were less effective as an antimalarial and more toxic (IC range: 14.67-81.24μM) than quinine (IC: 275.6±16.46μM) against the human kidney epithelial cells. None of the compounds exhibited any inhibitory effect on the viability of Anopheles arabiensis mosquito larvae.
为了开发有效的抗原虫药物，合成了4-(7-氯喹啉-4-基)哌嗪-1-基)吡咯烷-2-基)甲酮衍生物(5-14)，对其进行了表征并对其抗原虫活性进行了生物学评价。这些化合物在体外针对溶组织内阿米巴的HM1:IMSS菌株和恶性疟原虫的NF54氯喹敏感菌株进行了筛选。在合成的化合物中，有六种表现出有前景的抗阿米巴活性，其IC值(0.14-1.26μM)低于标准药物甲硝唑(IC 1.80μM)。所有九种化合物均表现出抗疟活性(IC范围:1.42-19.62μM)，同时对宿主红细胞保持良好的安全性。所有化合物作为抗疟药的效果均不如奎宁(IC:275.6±16.46μM)，且对人肾上皮细胞的毒性更大(IC范围:14.67-81.24μM)。没有一种化合物对阿拉伯按蚊幼虫的活力表现出任何抑制作用。
