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Glycosidation of lupane-type triterpenoids as potent in vitro cytotoxic agents.
Bioorg Med Chem. 2006 Oct 01; 14(19):6713-25.BM

Abstract

The weak hydrosolubility of betulinic acid (3) hampers the clinical development of this natural anticancer agent. In order to circumvent this problem and to enhance the pharmacological properties of betulinic acid (3) and the lupane-type triterpenes lupeol (1), betulin (2), and methyl betulinate (7), glycosides (beta-D-glucosides, alpha-L-rhamnosides, and alpha-D-arabinosides) were synthesized and in vitro tested for cytotoxicity against three cancerous (A-549, DLD-1, and B16-F1) and one healthy (WS1) cell lines. The addition of a sugar moiety at the C-3 or C-28 position of betulin (2) resulted in a loss of cytotoxicity. In contrast, the 3-O-beta-D-glucosidation of lupeol (1) improved the activity by 7- to 12-fold (IC50 14-15.0 microM). Moreover, the results showed that cancer cell lines are 8- to 12-fold more sensitive to the 3-O-alpha-L-rhamnopyranoside derivative of betulinic acid (IC50 2.6-3.9 microM, 22) than the healthy cells (IC50 31 microM). Thus, this study indicates that 3-O-glycosides of lupane-type triterpenoids represent an interesting class of potent in vitro cytotoxic agents.

Authors+Show Affiliations

Laboratoire LASEVE, Département des Sciences Fondamentales, UQAC, Chicoutimi, Québec, Canada G7H 2B1.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16787747

Citation

Gauthier, Charles, et al. "Glycosidation of Lupane-type Triterpenoids as Potent in Vitro Cytotoxic Agents." Bioorganic & Medicinal Chemistry, vol. 14, no. 19, 2006, pp. 6713-25.
Gauthier C, Legault J, Lebrun M, et al. Glycosidation of lupane-type triterpenoids as potent in vitro cytotoxic agents. Bioorg Med Chem. 2006;14(19):6713-25.
Gauthier, C., Legault, J., Lebrun, M., Dufour, P., & Pichette, A. (2006). Glycosidation of lupane-type triterpenoids as potent in vitro cytotoxic agents. Bioorganic & Medicinal Chemistry, 14(19), 6713-25.
Gauthier C, et al. Glycosidation of Lupane-type Triterpenoids as Potent in Vitro Cytotoxic Agents. Bioorg Med Chem. 2006 Oct 1;14(19):6713-25. PubMed PMID: 16787747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glycosidation of lupane-type triterpenoids as potent in vitro cytotoxic agents. AU - Gauthier,Charles, AU - Legault,Jean, AU - Lebrun,Maxime, AU - Dufour,Philippe, AU - Pichette,André, Y1 - 2006/06/19/ PY - 2006/05/01/received PY - 2006/05/26/revised PY - 2006/05/30/accepted PY - 2006/6/22/pubmed PY - 2006/11/7/medline PY - 2006/6/22/entrez SP - 6713 EP - 25 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 14 IS - 19 N2 - The weak hydrosolubility of betulinic acid (3) hampers the clinical development of this natural anticancer agent. In order to circumvent this problem and to enhance the pharmacological properties of betulinic acid (3) and the lupane-type triterpenes lupeol (1), betulin (2), and methyl betulinate (7), glycosides (beta-D-glucosides, alpha-L-rhamnosides, and alpha-D-arabinosides) were synthesized and in vitro tested for cytotoxicity against three cancerous (A-549, DLD-1, and B16-F1) and one healthy (WS1) cell lines. The addition of a sugar moiety at the C-3 or C-28 position of betulin (2) resulted in a loss of cytotoxicity. In contrast, the 3-O-beta-D-glucosidation of lupeol (1) improved the activity by 7- to 12-fold (IC50 14-15.0 microM). Moreover, the results showed that cancer cell lines are 8- to 12-fold more sensitive to the 3-O-alpha-L-rhamnopyranoside derivative of betulinic acid (IC50 2.6-3.9 microM, 22) than the healthy cells (IC50 31 microM). Thus, this study indicates that 3-O-glycosides of lupane-type triterpenoids represent an interesting class of potent in vitro cytotoxic agents. SN - 0968-0896 UR - https://www.unboundmedicine.com/medline/citation/16787747/Glycosidation_of_lupane_type_triterpenoids_as_potent_in_vitro_cytotoxic_agents_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(06)00452-4 DB - PRIME DP - Unbound Medicine ER -