Betulin and ursolic acid synthetic derivatives as inhibitors of Papilloma virus.
The synthesis of new betulin and ursolic acid derivatives and evaluation of their antiviral activity in vitro is reported. Betulin was modified at positions C-3, C-20 and C-28 to afford the derivatives with nicotinoyl-, methoxycynnamoyl-, alkyne and aminopropoxy-2-cyanoethyl-moieties. The two stage conversion of betulin to the new ursane-type triterpenoid by treatment of allobetulin with Ac(2)O-HClO(4) is suggested. Cyanoethylation of ursonic acid oxime led to cyanoethyloximinoderivative. According to the results of antiviral screening against human papillomavirus type 11 the selectivity index for tested triterpenoids has a range from 10 to 35 with no cellular cytotoxicity, the most remarkable activity was found for 3beta,28-di-O-nicotinoylbetulin. 3Beta,28-dihydroxy-29-norlup-20(30)-yne was also active against HCV replicon (EC(50) 1.32; EC(90) 16.82; IC(50) 12.41; IC(90) >20; SI(50) 9.4; SI(90) >1.19). 28-O-methoxycynnamoylbetulin was active against influenza type A virus (H1N1) (EC(50) 2; IC(50) >200; SI >100).
Kazakova
Oxana B
OB
Institute of Organic Chemistry, Ufa Research Center of the Russian Academy of Sciences, 71, Prospect Oktyabrya, 450054 Ufa, Russian Federation. obf@anrb.ru
Giniyatullina
Gul'nara V
GV
Yamansarov
Emil Yu
EY
Tolstikov
Genrikh A
GA
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D027383:Papillomaviridae / Q000187:drug effects*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D000097245:Ursolic Acid; D000094062:Betulinic Acid
D000998:Antiviral Agents; D014315:Triterpenes; D000097245:Ursolic Acid; C002503:betulin; D000094062:Betulinic Acid