Exploring clotrimazole-based pharmacophore: 3D-QSAR studies and synthesis of novel antiplasmodial agents

被引：12

作者：

Brogi, Simone ^{[1
,2
,3
]}

Brindisi, Margherita ^{[1
,2
,3
]}

Joshi, Bhupendra P. ^{[1
,2
]}

Coccone, Salvatore Sanna ^{[1
,2
]}

Parapini, Silvia ^{[1
,3
,4
]}

Basilico, Nicoletta ^{[1
,3
,5
]}

Novellino, Ettore ^{[1
,6
]}

Campiani, Giuseppe ^{[1
,2
,3
]}

Gemma, Sandra ^{[1
,2
,3
]}

Butini, Stefania ^{[1
,2
,3
]}

机构：

[1] Univ Siena, European Res Ctr Drug Discovery & Dev NatSynDrugs, I-53100 Siena, Italy

[2] Univ Siena, Dipartimento Biotecnol Chim & Farm, I-53100 Siena, Italy

[3] Univ Perugia, CIRM, I-06100 Perugia, Italy

[4] Univ Milan, Dipartimento Sci Farmacol & Biomol, I-20133 Milan, Italy

[5] Univ Milan, Dipartimento Sci Biomed Chirurg & Odontoiatr, I-20133 Milan, Italy

[6] Univ Naples Federico II, Dipartimento Farm, I-80131 Naples, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 22期

关键词：

Malaria; Plasmodium falciparum; Clotrimazole; 3D-QSAR; Ligand-based; POTENT ANTIMALARIAL AGENTS; PLASMODIUM-FALCIPARUM; INNOVATIVE PHARMACOPHORE; ARTEMISININ RESISTANCE; INHIBITORS; DESIGN; DISCOVERY; SCAFFOLD; PFSUB1;

D O I：

10.1016/j.bmcl.2015.09.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2015 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5412 / 5418

页数：7

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