New pentasubstituted pyrrole hybrid atorvastatin–quinoline derivatives with antiplasmodial activity. Issue 8 (15th April 2016)

• Record Type: Journal Article
• Authors: Carvalho, Rita C.C.; Martins, Wagner A.; Silva, Tayara P.; Kaiser, Carlos R.; Bastos, Mônica M.; Pinheiro, Luiz C.S.; Krettli, Antoniana U.; Boechat, Núbia
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 8(2016)
• Page Start: 1881
• Page End: 1884
• Publication Date: 2016-04-15
• Subjects: Malaria -- Atorvastatin -- Pentasubstituted pyrrole -- Chloroquine -- Primaquine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.03.027
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Cerebral malaria is caused by Plasmodium falciparum . Atorvastatin (AVA) is a pentasubstituted pyrrole, which has been tested as an adjuvant in the treatment of cerebral malaria. Herein, a new class of hybrids of AVA and aminoquinolines (primaquine and chloroquine derivatives) has been synthesized. The quinolinic moiety was connected to the pentasubstituted pyrrole from AVA by a linker group (CH2 ) n = 2–4 units. The activity of the compounds increased with the size of the carbons chain. Compound with n = 4 and 7-chloroquinolinyl has displayed better activity (IC50 = 0.40 μM) than chloroquine. The primaquine derivative showed IC50 = 1.41 μM, being less toxic and more active than primaquine.