Novel N-(4-Piperidinyl)benzamide antimalarials with mammalian protein farnesyltransferase inhibitory activity.
Protein farnesyltransferase of Plasmodium falciparum is a potential target in the treatment of malaria for which increased drug resistance is observed. The design, synthesis and evaluation of a series of N-(4-piperidinyl)benzamides is reported. The most potent compounds showed in vitro activity against the parasite at submicromolar concentrations.
Ryckebusch
Adina
A
Institut de Chimie Pharmaceutique Albert Lespagnol, EA 2692, Université de Lille 2, France.
Gilleron
Pauline
P
Millet
Régis
R
Houssin
Raymond
R
Lemoine
Amélie
A
Pommery
Nicole
N
Grellier
Philippe
P
Sergheraert
Christian
C
Hénichart
Jean-Pierre
JP
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
D000962:Antimalarials; D001549:Benzamides; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase