Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1917-1926 |
| Number of pages | 10 |
| Journal | Journal of Natural Products |
| Volume | 72 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2009 |
| MoE publication type | A1 Journal article-refereed |
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Betulin-derived compounds as inhibitors of alphavirus replication. / Pohjala, L.; Alakurtti, Sami; Ahola, T.; Yli-Kauhaluoma, Jari; Tammela, P. (Corresponding Author).
In: Journal of Natural Products, Vol. 72, No. 11, 2009, p. 1917-1926.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Betulin-derived compounds as inhibitors of alphavirus replication
AU - Pohjala, L.
AU - Alakurtti, Sami
AU - Ahola, T.
AU - Yli-Kauhaluoma, Jari
AU - Tammela, P.
PY - 2009
Y1 - 2009
N2 - This paper describes inhibition of Semliki Forest virus (SFV) replication by synthetic derivatives of naturally occurring triterpenoid betulin (1). Chemical modifications were made to OH groups at C-3 and C-28 and to the C-20−C-29 double bond. A set of heterocyclic betulin derivatives was also assayed. A free or acetylated OH group at C-3 was identified as an important structural contributor for anti-SFV activity, 3,28-di-O-acetylbetulin (4) being the most potent derivative (IC50 value 9.1 μM). Betulinic acid (13), 28-O-tetrahydropyranylbetulin (17), and a triazolidine derivative (41) were also shown to inhibit Sindbis virus, with IC50 values of 0.5, 1.9, and 6.1 μM, respectively. The latter three compounds also had significant synergistic effects against SFV when combined with 3′-amino-3′-deoxyadenosine. In contrast to previous work on other viruses, the antiviral activity of 13 was mapped to take place in virus replication phase. The efficacy was also shown to be independent of external guanosine supplementation.
AB - This paper describes inhibition of Semliki Forest virus (SFV) replication by synthetic derivatives of naturally occurring triterpenoid betulin (1). Chemical modifications were made to OH groups at C-3 and C-28 and to the C-20−C-29 double bond. A set of heterocyclic betulin derivatives was also assayed. A free or acetylated OH group at C-3 was identified as an important structural contributor for anti-SFV activity, 3,28-di-O-acetylbetulin (4) being the most potent derivative (IC50 value 9.1 μM). Betulinic acid (13), 28-O-tetrahydropyranylbetulin (17), and a triazolidine derivative (41) were also shown to inhibit Sindbis virus, with IC50 values of 0.5, 1.9, and 6.1 μM, respectively. The latter three compounds also had significant synergistic effects against SFV when combined with 3′-amino-3′-deoxyadenosine. In contrast to previous work on other viruses, the antiviral activity of 13 was mapped to take place in virus replication phase. The efficacy was also shown to be independent of external guanosine supplementation.
U2 - 10.1021/np9003245
DO - 10.1021/np9003245
M3 - Article
VL - 72
SP - 1917
EP - 1926
JO - Journal of Natural Products
JF - Journal of Natural Products
SN - 0163-3864
IS - 11
ER -