Synthesis and Cytotoxicity of Bidesmosidic Betulin and Betulinic Acid Saponins

Abstract

The naturally occurring cytotoxic saponin 28-O-beta-d-glucopyranosylbetulinic acid 3beta-O-alpha-l-arabinopyranoside (3) was easily synthesized along with seven bidesmosidic saponins starting from the lupane-type triterpenoids betulin (1) and betulinic acid (2). As highlighted by the preliminary cytotoxicity evaluation against A549, DLD-1, MCF7, and PC-3 human cancer cell lines, the bidesmosidic betulin saponin 22a, bearing alpha-l-rhamnopyranoside moieties at both C-3 and C-28 positions, was determined to be a potent cytotoxic agent (IC(50) 1.8-1.9 microM).

Isolement, caractérisation et évaluation de l'activité antibactérienne de dérivés de dihydrochalcones hydroxycinnamylés issus de bourgeons de populus balsamifera L. /

“…These positive results prompted us to investigate in depth the cytotoxic potential of glycosylated lupane triterpenes by undertaking the preparation of bidesmosides (Gauthier et al 2008).…”

“…To obtain significant information about the SAR of lupane-type bidesmosides, seven other non-natural lupane bidesmosides bearing D-glucose, L-arabinose and L-rhamnose sugar moieties were also prepared starting from betulin (34) and betulinic acid (33). The syntheses were carried out by a combination of Schmidt's procedure and phase transfer conditions using fully benzoylated trichloroacetimidate and sugar bromide donors (Gauthier et al 2008). All bidesmosides were assayed against A549, DLD-1, MCF7 and PC-3 human cancer cell lines.…”

Chemistry and pharmacology of saponins: special focus on cytotoxic properties

“…There have been sporadic reports on the structure-activity relationship, providing a possible correlation between the cytotoxic effects and certain structural features. Readers are referred to some interesting research by Gauthier et al 24,32,33 In a recent study by Liu et al, a synthetic derivative of β-hederin was evaluated for its cytotoxic properties in five human cell lines (ie, HeLa, MCF-7, HL-60, HT1080, and Hep-G2). 34 The authors reported synthesis of 13 novel triterpenoid saponins, designed as amide derivatives of the natural cytotoxic saponin, β-hederin, using a stepwise glycosylation strategy.…”

“…Similarly, Gauthier et al have evaluated the lupane-type and oleanane-type saponins from a structureactivity-relationship perspective. 24,33 Numerous human cell lines were tested, including lung carcinoma, and also normal skin fibroblasts. In the case of oleanane-type saponins, the oleanolic acid derivatives were by far the most active, while hederegenin saponins were not so active.…”

Contribuição da fitoquímica para o desenvolvimento de um país emergente

“…36 A importância do ácido betulínico (67) estimulou o desenvolvimento de novas atividades de pesquisa na busca, inclusive, de produtos derivados dotados de outras atividades biológicas através de biotransformações químicas 37 ou utilizando, inclusive, novos reagentes e novas reações. [38][39][40][41] Transformações microbiológicas (biotransformações, Esquema 6) para obtenção de substâncias mais ativas e/ou menos tóxicas assumem interesse social e econômico, principalmente quando tais conversões seletivas através de modificações sintéticas revelam dificuldades (Esquema 6). 37 As transformações microbiológicas de substâncias naturais e sintéticas oferecem novos horizontes para modificações estruturais destinadas a vários objetivos, desde a introdução de grupos funcionais a rearranjos moleculares.…”