探索基于克霉唑的药效团：3D-QSAR研究及新型抗疟药的合成
Exploring clotrimazole-based pharmacophore: 3D-QSAR studies and synthesis of novel antiplasmodial agents.
作者信息
Brogi Simone, Brindisi Margherita, Joshi Bhupendra P, Sanna Coccone Salvatore, Parapini Silvia, Basilico Nicoletta, Novellino Ettore, Campiani Giuseppe, Gemma Sandra, Butini Stefania
机构信息
European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Centro Interuniversitario di Ricerche sulla Malaria (CIRM), University of Perugia, Perugia, Italy.
European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy.
出版信息
Bioorg Med Chem Lett. 2015 Nov 15;25(22):5412-8. doi: 10.1016/j.bmcl.2015.09.007. Epub 2015 Sep 5.
We report herein the generation and validation of a 3D-QSAR model based on a set of antimalarials previously described by us and characterized by a clotrimazole-based pharmacophore. A novel series of derivatives was synthesized and showed activity against Plasmodium falciparum chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains. Gratifyingly, compounds 35a-c showed interesting activity against P. falciparum CQ-R strains with improved predicted physico-chemical properties.
我们在此报告基于我们之前描述的一组抗疟药生成并验证的3D-QSAR模型，这些抗疟药以克霉唑基药效团为特征。合成了一系列新型衍生物，它们对恶性疟原虫氯喹敏感（CQ-S）和氯喹耐药（CQ-R）菌株均显示出活性。令人欣慰的是，化合物35a-c对恶性疟原虫CQ-R菌株表现出有趣的活性，且预测的物理化学性质有所改善。
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