title: Synthesis and evaluation of A-seco type triterpenoids for anti-HIV-1protease activity.
abstract: 2,3-Seco-dioic acids derived from four different triterpene skeletons were prepared and evaluated for their anti-HIV-1 protease activity. Two A-seco derivatives showed potent inhibitory activity against HIV-1 protease (3c and 3e, IC(50) 5.7 and 3.9 microM, respectively), while four other derivatives showed moderate to weak inhibition (3a, 3b, 3d and 3f, IC(50) 15.7-88.1 microM). The combination of a 2,3-seco-2,3-dioic acid functional group in ring A and a free acid group at C-28 or C-30 significantly enhanced HIV-1 protease inhibitory activity (3a, 3c-3e, IC(50) 3.9-17.6 microM). On the other hand, all A-seco derivatives were found to be very weak inhibitors of HCV, renin and trypsin proteases (IC(50)>80 microM). These findings indicate that A-seco triterpenes with a carboxyl group at C-28 or C-30 are novel and highly selective HIV-1 protease inhibitors.
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wei
authors.forename: Chao-Mei
authors.initials: CM
authors.lastname: Ma
authors.forename: Masao
authors.initials: M
authors.lastname: Hattori
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology; D016174:Hepacivirus / Q000201:enzymology; D012083:Renin / Q000378:metabolism; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D014315:Triterpenes; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; D012083:Renin