Quinolin-4(1H)‑imines are Potent Antiplasmodial Drugs Targeting the Liver Stage of Malaria

• Published in: Journal of medicinal chemistry Vol. 56; no. 11; pp. 4811 - 4815
• Main Authors: Rodrigues, Tiago, da Cruz, Filipa P, Lafuente-Monasterio, Maria J, Gonçalves, Daniel, Ressurreição, Ana S, Sitoe, Ana R, Bronze, Maria R, Gut, Jiri, Schneider, Gisbert, Mota, Maria M, Rosenthal, Philip J, Prudêncio, Miguel, Gamo, Francisco-Javier, Lopes, Francisca, Moreira, Rui
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 13.06.2013; Amer Chemical Soc
• Subjects: Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Cell Line, Tumor; Chemistry, Medicinal; Humans; Imines - chemical synthesis; Imines - chemistry; Imines - pharmacology; Life Sciences & Biomedicine; Liver - drug effects; Liver - parasitology; Malaria - drug therapy; Parasitic Sensitivity Tests; Pharmacology & Pharmacy; Plasmodium berghei - drug effects; Plasmodium falciparum - drug effects; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Science & Technology; Structure-Activity Relationship; PARASITES; THOUSANDS; QUINOLONES; MITOCHONDRIAL ELECTRON-TRANSPORT; PLASMODIUM; SUBSTITUENT CONSTANTS; OPTIMIZATION; GENERATION; ANTIMALARIALS; INHIBITORS
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm400246e

We present a novel series of quinolin-4(1H)-imines as dual-stage antiplasmodials, several-fold more active than primaquine in vitro against Plasmodium berghei liver stage. Among those, compounds 5g and 5k presented low nanomolar IC50 values. The compounds are metabolically stable and modulate several drug targets. These results emphasize the value of quinolin-4(1H)-imines as a new chemotype and their suitable properties for further drug development.