In vitro evaluation of imidazo[4,5-c]quinolin-2-ones as gametocytocidal antimalarial agents

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:26

Article

Patel, Paresma R.^1,3  Sun, Wei¹  Kim, Myunghoon¹  Huang, Xiuli¹  Sanderson, Philip E.¹  Tanaka, Takeshi Q.^2,4  McKew, John C.^1,5  Simeonov, Anton¹  Williamson, Kim C.^2,6  Zheng, Wei¹  Huang, Wenwei¹ 

[1] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA

[2] Loyola Univ, Dept Biol, Chicago, IL 60660 USA

[3] US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA

[4] Obihiro Univ Agr & Vet Med, Natl Res Ctr Protozoan Dis, Obihiro, Hokkaido 0808555, Japan

[5] aTyr Pharma Inc, 3545 John Hopkins Court,Suite 250, San Diego, CA 92121 USA

[6] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA

关键词: Antimalarial;    Plasmodium falciparum;    Gametocytes;    Gametocytocidal;    Imidazo[4,5-c]quinolin-2-one;   

DOI  :  10.1016/j.bmcl.2016.04.045

来源: Elsevier

【 摘 要 】

Novel imidazo[4,5-c] quinolin-2-ones were synthesized and evaluated in asexual blood stage and late stage gametocyte assays of Plasmodium falciparum, a major causative agent of malaria. The design of these compounds is based on a recently identified lead compound from a high throughput screen. A concise synthesis was developed that allowed for generation of analogues with substitution around both the quinoline and imidazolidinone rings. Through structure-activity relationship studies, a number of potent compounds were identified that possessed excellent antimalarial activity against both the asexual and sexual stages with minimal cytotoxicity in mammalian cells. This is the first Letter describing SAR and gametocytocidal activity of imidazo[4,5-c] quinolin-2-ones, a new lead series for malaria treatment and prevention. Published by Elsevier Ltd.

【 授权许可】

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