Sulfonyl-phenyl-ureido benzamidines; a novel structural class of potent antimalarial agents.
The high throughput in silico screening of a virtual library into the structure of the P. falciparum lactate dehydrogenase (LDH) with the 4SCan technology yielded a series of biphenyl urea compounds. These were chemically optimized to a new structural class of potent antimalarial agents. The compounds did not inhibit plasmodium LDH enough to fully explain their potency. Therefore we conclude that an unknown mode of action may be the cause of the antimalarial activity.
Leban
Johann
J
4SC AG, Am Klopferspitz 19a, 82152 Martinsried, Germany. leban@4sc.com
Pegoraro
Stefano
S
Dormeyer
Matthias
M
Lanzer
Michael
M
Aschenbrenner
Andrea
A
Kramer
Bernd
B
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001550:Benzamidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000962:Antimalarials; D001550:Benzamidines; D015800:Protozoan Proteins; D007770:L-Lactate Dehydrogenase