Betulin-derived compounds as inhibitors of alphavirus replication

L. Pohjala, Sami Alakurtti, T. Ahola, Jari Yli-Kauhaluoma, P. Tammela (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

63 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1917-1926
Number of pages10
JournalJournal of Natural Products
Volume72
Issue number11
DOIs
Publication statusPublished - 2009
MoE publication typeA1 Journal article-refereed

Fingerprint

Semliki forest virus
Alphavirus
Viruses
Virus Replication
Inhibitory Concentration 50
Sindbis Virus
Derivatives
Guanosine
Antiviral Agents
Chemical modification
betulin

Cite this

Pohjala, L., Alakurtti, S., Ahola, T., Yli-Kauhaluoma, J., & Tammela, P. (2009). Betulin-derived compounds as inhibitors of alphavirus replication. Journal of Natural Products, 72(11), 1917-1926. https://doi.org/10.1021/np9003245
Pohjala, L. ; Alakurtti, Sami ; Ahola, T. ; Yli-Kauhaluoma, Jari ; Tammela, P. / Betulin-derived compounds as inhibitors of alphavirus replication. In: Journal of Natural Products. 2009 ; Vol. 72, No. 11. pp. 1917-1926.
@article{d339c4677e5743a0adb2f0bdcfcc7d97,
title = "Betulin-derived compounds as inhibitors of alphavirus replication",
abstract = "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.",
author = "L. Pohjala and Sami Alakurtti and T. Ahola and Jari Yli-Kauhaluoma and P. Tammela",
year = "2009",
doi = "10.1021/np9003245",
language = "English",
volume = "72",
pages = "1917--1926",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society ACS",
number = "11",

}

Pohjala, L, Alakurtti, S, Ahola, T, Yli-Kauhaluoma, J & Tammela, P 2009, 'Betulin-derived compounds as inhibitors of alphavirus replication', Journal of Natural Products, vol. 72, no. 11, pp. 1917-1926. https://doi.org/10.1021/np9003245

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 journalArticleScientificpeer-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 -

Pohjala L, Alakurtti S, Ahola T, Yli-Kauhaluoma J, Tammela P. Betulin-derived compounds as inhibitors of alphavirus replication. Journal of Natural Products. 2009;72(11):1917-1926. https://doi.org/10.1021/np9003245