New pentasubstituted pyrrole hybrid atorvastatin–quinoline derivatives with antiplasmodial activity

• Published in: Bioorganic & medicinal chemistry letters Vol. 26; no. 8; pp. 1881 - 1884
• Main 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
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.04.2016; Elsevier
• Subjects: Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Atorvastatin; Atorvastatin Calcium - chemistry; Atorvastatin Calcium - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Chloroquine; Dose-Response Relationship, Drug; Life Sciences & Biomedicine; Malaria; Molecular Structure; Parasitic Sensitivity Tests; Pentasubstituted pyrrole; Pharmacology & Pharmacy; Physical Sciences; Plasmodium falciparum; Plasmodium falciparum - drug effects; Primaquine; Pyrroles - chemistry; Pyrroles - pharmacology; Quinolines - chemistry; Quinolines - pharmacology; Science & Technology; Structure-Activity Relationship; Atorvastatin; Pentasubstituted pyrrole; Malaria; Primaquine; Chloroquine; ANTIMALARIAL-DRUGS; IN-VITRO; TRISUBSTITUTED PYRROLE; PLASMODIUM; MEFLOQUINE; STATINS; CEREBRAL MALARIA
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.03.027

[Display omitted] 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=0.40μM) than chloroquine. The primaquine derivative showed IC50=1.41μM, being less toxic and more active than primaquine.