Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russia.
Molecules. 2018 Nov 16;23(11):3000. doi: 10.3390/molecules23113000.
Triterpene acids, namely, 20,29-dihydrobetulinic acid (BA), ursolic acid (UA) and oleanolic acid (OA) were converted into C-28-amino-functionalized triterpenoids ⁻, , , and . These compounds served as precursors for the synthesis of novel guanidine-functionalized triterpene acid derivatives ⁻, , and . 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 , , , and , irrespective of the triterpene skeleton type. The dihydrobetulinic acid amine , its guanidinium derivative and guanidinium derivatives of ursolic and oleanolic acids and 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.
三萜酸，即 20,29-二氢白桦酸（BA）、熊果酸（UA）和齐墩果酸（OA）被转化为 C-28-氨基功能化的三萜类化合物 ⁻ 、 、 、 和 。这些化合物作为合成新型胍基功能化三萜酸衍生物 ⁻ 、 、 和 的前体。研究了胍基对三萜类化合物抗肿瘤特性的影响。在五种人类肿瘤细胞系（Jurkat、K562、U937、HEK 和 Hela）上测试了细胞毒性，并与正常人类成纤维细胞的测试进行了比较。与相应的胺相比，大多数测试的胍衍生物的抗肿瘤活性较低，但具有胍基的三萜类化合物对人成纤维细胞的毒性较小。将三（羟甲基）氨基甲烷部分引入三萜酸分子中，显著增强了所得缀合物 ⁻ 、 、 、 和 的细胞毒性活性，而与三萜骨架类型无关。选择二氢白桦酸胺 、其胍衍生物 和熊果酸和齐墩果酸的胍衍生物 和 进行 Jurkat 细胞的扩展生物学研究，结果表明这些化合物的抗肿瘤活性是通过诱导 S 期细胞周期停滞和细胞凋亡介导的。
