Design, synthesis, and biological evaluation of new (2E,6E)-10-(dimethylamino)-3,7-dimethyl-2,6-decadien-1-ol ethers as inhibitors of human and Trypanosoma cruzi oxidosqualene cyclase.
New dimethylamino truncated squalene ether derivatives containing a different aromatic moiety (phenyl, naphthyl, and biphenyl) or a simple alkyl (n-hexylic) group were synthesized as inhibitors of the oxidosqualene cyclase (OSC) and of the sterol biosynthetic pathway. The activity against human OSC was compared with the activity against the OSCs of pathogenic organisms such as Pneumocystis carinii and Trypanosoma cruzi. The phenyl derivative was the most potent inhibitor of T. cruzi OSC.
Galli
Ubaldina
U
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche and Drug and Food Biotechnology Center, Università degli Studi del Piemonte Orientale A. Avogadro, Via Bovio 6, 28100 Novara, Italy. galli@pharm.unipmn.it
Oliaro-Bosso
Simonetta
S
Taramino
Silvia
S
Venegoni
Serena
S
Pastore
Emanuele
E
Tron
Gian Cesare
GC
Balliano
Gianni
G
Viola
Franca
F
Sorba
Giovanni
G
D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors*; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013185:Squalene / Q000031:analogs & derivatives*; D014349:Trypanosoma cruzi / Q000201:enzymology*
D000977:Antiparasitic Agents; D004791:Enzyme Inhibitors; D010647:Phenyl Ethers; D013185:Squalene; D019751:Intramolecular Transferases; C021924:lanosterol synthase