肼基酞嗪对疟原虫恶性疟原虫的合成及体外评价
Synthesis and in vitro evaluation of hydrazinyl phthalazines against malaria parasite, Plasmodium falciparum.
作者信息
Subramanian Gowtham, Babu Rajeev C P, Mohan Chakrabhavi Dhananjaya, Sinha Ameya, Chu Trang T T, Anusha Sebastian, Ximei Huang, Fuchs Julian E, Bender Andreas, Rangappa Kanchugarakoppal S, Chandramohanadas Rajesh
机构信息
Pillar of Engineering Product Development, Singapore University of Technology & Design, Singapore 487372, Singapore.
Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore 560001, India.
出版信息
Bioorg Med Chem Lett. 2016 Jul 15;26(14):3300-3306. doi: 10.1016/j.bmcl.2016.05.049. Epub 2016 May 18.
In this report, we describe the synthesis of 1-(Phthalazin-4-yl)-hydrazine using bronsted acidic ionic liquids and demonstrate their ability to inhibit asexual stage development of human malaria parasite, Plasmodium falciparum. Through computational studies, we short-listed chemical scaffolds with potential binding affinity to an essential parasite protein, dihydroorotate dehydrogenase (DHODH). Further, these compounds were synthesized in the lab and tested against P. falciparum. Several compounds from our library showed inhibitory activity at low micro-molar concentrations with minimal cytotoxic effects. These results indicate the potential of hydralazine derivatives as reference scaffolds to develop novel antimalarials.
在本报告中，我们描述了使用布朗斯台德酸性离子液体合成1-(酞嗪-4-基)肼，并证明了它们抑制人类疟原虫恶性疟原虫无性阶段发育的能力。通过计算研究，我们筛选出了与一种重要的寄生虫蛋白二氢乳清酸脱氢酶（DHODH）具有潜在结合亲和力的化学骨架。此外，这些化合物在实验室中合成并针对恶性疟原虫进行了测试。我们文库中的几种化合物在低微摩尔浓度下显示出抑制活性，且细胞毒性极小。这些结果表明肼衍生物作为开发新型抗疟药物的参考骨架具有潜力。
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