| Summary: | Triterpene acids, namely, 20,29-dihydrobetulinic acid (BA), ursolic acid (UA) and oleanolic acid (OA) were converted into C-28-amino-functionalized triterpenoids <b>4</b>⁻<b>7</b>, <b>8a</b>, <b>15</b>, <b>18</b> and <b>20</b>. These compounds served as precursors for the synthesis of novel guanidine-functionalized triterpene acid derivatives <b>9b</b>⁻<b>12b</b>, <b>15c</b>, <b>18c</b> and <b>20c</b>. The influence of the guanidine group on the antitumor properties of triterpenoids was investigated. The cytotoxicity was tested on five human tumor cell lines (Jurkat, K562, U937, HEK, and Hela), and compared with the tests on normal human fibroblasts. The antitumor activities of the most tested guanidine derivatives was lower, than that of corresponding amines, but triterpenoids with the guanidine group were less toxic towards human fibroblasts. The introduction of the tris(hydroxymethyl)aminomethane moiety into the molecules of triterpene acids markedly enhanced the cytotoxic activity of the resulting conjugates <b>15</b>, <b>15c</b>, <b>18b</b>,<b>c</b> and <b>20b</b>,<b>c</b> irrespective of the triterpene skeleton type. The dihydrobetulinic acid amine <b>15</b>, its guanidinium derivative <b>15c</b> and guanidinium derivatives of ursolic and oleanolic acids <b>18c</b> and <b>20c</b> were selected for extended biological investigations in Jurkat cells, which demonstrated that the antitumor activity of these compounds is mediated by induction of cell cycle arrest at the S-phase and apoptosis.
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