DesignMedix, Inc., Portland, OR 97201, USA.
Department of Chemistry, Portland State University, Portland, OR 97207, USA.
Molecules. 2020 May 10;25(9):2251. doi: 10.3390/molecules25092251.
Quinoline-based scaffolds have been the mainstay of antimalarial drugs, including many artemisinin combination therapies (ACTs), over the history of modern drug development. Although much progress has been made in the search for novel antimalarial scaffolds, it may be that quinolines will remain useful, especially if very potent compounds from this class are discovered. We report here the results of a structure-activity relationship (SAR) study assessing potential unsymmetrical bisquinoline antiplasmodial drug candidates using in vitro activity against intact parasites in cell culture. Many unsymmetrical bisquinolines were found to be highly potent against both chloroquine-sensitive and chloroquine-resistant parasites. Further work to develop such compounds could focus on minimizing toxicities in order to find suitable candidates for clinical evaluation.
喹啉类化合物一直是抗疟药物的主要结构骨架，包括许多青蒿素类复方疗法（ACT），这在现代药物开发的历史中占据着重要地位。尽管在寻找新型抗疟药物骨架方面已经取得了很大进展，但喹啉类化合物可能仍然有用，特别是如果从这类化合物中发现非常有效的化合物。我们在此报告了一项结构-活性关系（SAR）研究的结果，该研究使用细胞培养中完整寄生虫的体外活性评估了潜在的非对称双喹啉抗疟药物候选物。许多非对称双喹啉类化合物对氯喹敏感和氯喹耐药寄生虫均具有很高的活性。进一步开发此类化合物的工作可以集中在降低毒性，以找到适合临床评估的候选药物。
