Gul H I, Vepsalainen J, Gul M, Erciyas E, Hanninen O
Department of Chemistry, University of Kuopio, Finland.
Pharm Acta Helv. 2000 Apr;74(4):393-8. doi: 10.1016/s0031-6865(00)00022-4.
Mannich bases of acetophenones have been disclosed to have antitumour and cytotoxic activities. 1-Phenyl-3-dimethylaminopropan-1-one hydrochloride, 1, and related piperidino, 2, and morpholino, 3, derivatives, and compound 4, which is a quaternary form of 1, were synthesized as mono Mannich bases derived from acetophenone. They were converted to corresponding bis Mannich bases, 5-8, to see whether it increases the bioactivity. The biological activity of the compounds was examined by cytotoxicity against mouse renal carcinoma (Renca) and transformed human T-lymphocyte (Jurkat) cell lines. Conversion of mono Mannich bases to corresponding bis Mannich bases remarkably increased the cytotoxicity in most cases. Quaternization procedure also improved the bioactivity in mono derivatives against Jurkat cells. Bis mannich bases 5-7 were found to be more active than 5-fluorouracil (6-23 fold) and melphalan (1.25-5 fold) against Renca cells. Except 2 and 8, the compounds synthesised were found to be more active than 5-fluorouracil (1.2-33 fold) against Jurkat cells.
已披露苯乙酮的曼尼希碱具有抗肿瘤和细胞毒性活性。合成了1-苯基-3-二甲基氨基丙-1-酮盐酸盐（1）以及相关的哌啶基衍生物（2）、吗啉基衍生物（3），还有作为1的季铵盐形式的化合物4，它们均为由苯乙酮衍生的单曼尼希碱。将它们转化为相应的双曼尼希碱（5 - 8），以观察其是否能提高生物活性。通过针对小鼠肾癌（Renca）和人转化T淋巴细胞（Jurkat）细胞系的细胞毒性来检测这些化合物的生物活性。在大多数情况下，单曼尼希碱转化为相应的双曼尼希碱会显著提高细胞毒性。季铵化过程也提高了单衍生物对Jurkat细胞的生物活性。发现双曼尼希碱5 - 7对Renca细胞的活性比5-氟尿嘧啶高（6 - 23倍），比美法仑高（1.25 - 5倍）。除2和8外，合成的化合物对Jurkat细胞的活性比5-氟尿嘧啶高（1.2 - 33倍）。
