Method of preparing and use of prodrugs of betulinic acid derivatives
a technology of betulinic acid and derivatives, which is applied in the field of compositions and methods of inhibiting tumors, can solve the problems of difficult production of betulinic acid-containing pharmacological formulations, and achieve the effects of preventing or inhibiting tumor growth, preventing or inhibiting the growth of malignant tumors, and improving the bioavailability of betulinic acid
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[0029] Betulinic acid, 3β-hydroxy-lup-20(29)-ene-28-oic acid, is a natural, pentacyclic triterpene product isolated from several genus of higher plants. Betulinic acid has demonstrated remarkable selective antitumor activity against human melanoma (E. Pisha et al., Nature Medicine, 1, pp. 1046-1051 (1995)) and anti-HIV activity (T. Fujioka et al., J. Nat. Prod., 57, pp. 243-247 (1994)).
[0030] Through a bioassay-directed fractionation of the stem bark of Ziziphus mauritiana Lam. (Rhamnaceae), betulinic acid was isolated as an active compound that showed a cytotoxicity against cultured human melanoma cells. Betulinic acid was found to be an excellent antitumor compound against human melanoma due to its unique in vitro and in vivo cytotoxicity profile. Betulinic acid showed a strong selective antitumor activity against melanoma by induction of apoptosis.
[0031] Betulinic acid also was found to have activity against the other cancer cell lines that were tested. The cytotoxicity of betu...
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