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DOI 10.1021/acs.jmedchem.0c00539

Медицинская библиотека · Journal of medicinal chemistry · 2020

Lead Optimization of Second-Generation Acridones as Broad-Spectrum Antimalarials.

Kancharla Papireddy, Dodean Rozalia A, Li Yuexin, Pou Sovitj, Pybus Brandon, Melendez Victor, Read Lisa, Bane Charles E, Vesely Brian, Kreishman-Deitrick Mara, Black Chad, Li Qigui, Sciotti Richard J, Olmeda Raul, Luong Thu-Lan, Gaona Heather, Potter Brittney, Sousa Jason, Marcsisin Sean, Caridha Diana, Xie Lisa, Vuong Chau, Zeng Qiang, Zhang Jing, Zhang Ping, Lin Hsiuling, Butler Kirk, Roncal Norma, Gaynor-Ohnstad Lacy, Leed Susan E, Nolan Christina, Ceja Frida G, Rasmussen Stephanie A, Tumwebaze Patrick K, Rosenthal Philip J, Mu Jianbing, Bayles Brett R, Cooper Roland A, Reynolds Kevin A, Smilkstein Martin J, Riscoe Michael K, Kelly Jane X

СтатьяПоддержка NIH: внешняя программаПоддержка правительства СШАПеревод пока не подготовлен

Аннотация

The global impact of malaria remains staggering despite extensive efforts to eradicate the disease. With increasing drug resistance and the absence of a clinically available vaccine, there is an urgent need for novel, affordable, and safe drugs for prevention and treatment of malaria. Previously, we described a novel antimalarial acridone chemotype that is potent against both blood-stage and liver-stage malaria parasites. Here, we describe an optimization process that has produced a second-generation acridone series with significant improvements in efficacy, metabolic stability, pharmacokinetics, and safety profiles. These findings highlight the therapeutic potential of dual-stage targeting acridones as novel drug candidates for further preclinical development.

Для цитирования: Kancharla Papireddy, Dodean Rozalia A, Li Yuexin, Pou Sovitj, Pybus Brandon, Melendez Victor, Read Lisa, Bane Charles E, Vesely Brian, Kreishman-Deitrick Mara, Black Chad, Li Qigui, Sciotti Richard J, Olmeda Raul, Luong Thu-Lan, Gaona Heather, Potter Brittney, Sousa Jason, Marcsisin Sean, Caridha Diana, Xie Lisa, Vuong Chau, Zeng Qiang, Zhang Jing, Zhang Ping, Lin Hsiuling, Butler Kirk, Roncal Norma, Gaynor-Ohnstad Lacy, Leed Susan E, Nolan Christina, Ceja Frida G, Rasmussen Stephanie A, Tumwebaze Patrick K, Rosenthal Philip J, Mu Jianbing, Bayles Brett R, Cooper Roland A, Reynolds Kevin A, Smilkstein Martin J, Riscoe Michael K, Kelly Jane X. Lead Optimization of Second-Generation Acridones as Broad-Spectrum Antimalarials.. Journal of medicinal chemistry. 2020. DOI: 10.1021/acs.jmedchem.0c00539.

Предметные рубрики MeSH

AcridonesAdministration, OralAnimalsAntimalarialsCell SurvivalDisease Models, AnimalFemaleHalf-LifeHep G2 CellsHumansLife Cycle StagesMalariaMaleMiceMice, Inbred C57BLPlasmodium falciparumStructure-Activity Relationship
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