2,4-Diarylthiazole antiprion compounds as a novel structural class of antimalarial leads

• Published in: Bioorganic & medicinal chemistry letters 2011-06, Vol.21 (12), p.3644-3647
• Main Authors: Thompson, Mark J., Louth, Jennifer C., Little, Susan M., Chen, Beining, Coldham, Iain
• Format: Article
• Language: English
• Subjects: Amines; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Antiparasitic agents; Biological and medical sciences; chemistry; chloroquine; Chloroquine - chemistry; Chloroquine - pharmacology; Dual activity; Malaria; Medical sciences; Mefloquine - chemistry; Mefloquine - pharmacology; Miscellaneous; Molecular Structure; Neuropharmacology; Pharmacology. Drug treatments; Plasmodium falciparum; Plasmodium falciparum - drug effects; Prion diseases; Prions - antagonists & inhibitors; quinacrine; Quinacrine - chemistry; Quinacrine - pharmacology; screening; Structure-Activity Relationship; Thiazoles; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.04.090

A significant intersection between antimalarial and antiprion activity is well established for certain compound classes, specifically for polycyclic antimalarial agents bearing basic nitrogen-containing sidechains (e.g., chloroquine, quinacrine, mefloquine). Screening a recently reported set of antiprion compounds with such sidechains showed these 2,4-diarylthiazole based structures also possess significant antimalarial activity. Of particular note, all but one of the compounds displayed activity against a chloroquine-resistant Plasmodium falciparum strain, identifying them as interesting leads for further development in this context. In addition, three new members of the series showed superior antiprion activity compared to the earlier-reported compounds.