Elomri A, Mitaku S, Michel S, Skaltsounis A L, Tillequin F, Koch M, Pierré A, Guilbaud N, Léonce S, Kraus-Berthier L, Rolland Y, Atassi G
Laboratoire de Pharmacognosie de l'Université René Descartes, URA au CNRS no. 1310, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
J Med Chem. 1996 Nov 22;39(24):4762-6. doi: 10.1021/jm9602975.
Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycine derivatives were more potent than acronycine itself when tested against L1210 cells in vitro. Four selected acronycine derivatives (17,19, 21, and 22) were evaluated in vivo against murine P388 leukemia and colon 38 adenocarcinoma implanted in mice. All compounds were markedly active against P388 at doses 4-16-fold lower than acronycine itself. Against the colon 38 adenocarcinoma, the three compounds 17, 21, and 22 were highly efficient. 1,2-Diacetoxy-1,2-dihydroacronycine (17) was the most active, all the treated mice being tumor-free on day 23.
通过对山油柑碱或6-去甲氧基山油柑碱进行锇酸氧化然后酰化，合成了七种1,2 - 二羟基 - 1,2 - 二氢山油柑碱以及1,2 - 二羟基 - 1,2 - 二氢 - 6 - 去甲氧基山油柑碱的酯和二酯。结果发现，6 - 去甲氧基山油柑碱衍生物无活性，而相比之下，所有山油柑碱衍生物在体外针对L1210细胞进行测试时，其活性均比山油柑碱本身更强。对四种选定的山油柑碱衍生物（17、19、21和22）进行了体内抗小鼠P388白血病以及植入小鼠体内的结肠38腺癌的评估。所有化合物在比山油柑碱本身低4至16倍的剂量下对P388均具有显著活性。对于结肠38腺癌，化合物17、21和22这三种表现出高效性。1,2 - 二乙酰氧基 - 1,2 - 二氢山油柑碱（17）活性最强，所有接受治疗的小鼠在第23天时均无肿瘤。
