Peng J, Su H D
Department of Biochemical Pharmacology, School of Pharmacy, Beijing Medical University.
Yao Xue Xue Bao. 1994;29(6):406-11.
Organotin compounds were found to obviously inhibit the activity of phospholipid/Ca(2+)-dependent protein kinase (PKC) in rat brain tissue and the proliferation of tumor cell lines in vitro. The results showed that a correlation exists between the effects on PKC and anti-proliferative and antitumor activities. The structure-activity relationship was shown to be as follows: (1) R, the organic group determines the biological activity; (2) electronegativity of the halogen can affect the activity. The organotin compounds inhibit tumor cells by its [SnR2]2+, and inhibit G1-->S phases of HL-60 cell cycle. The IC50 of [SnPh2F2], [SnPh2(CysOS)].H2O and [SnPh2Cl2.phen(CH3)2] are respectively 25, 15 and 20 mumol.L-1 on PKC, 0.5, 4.0 and 0.3 mumol.L-1 on HL-60 cells, 2.7, 9 and 1.5 mumol.L-1 on BEL-7402 cells, 2.2, 15 and 5.0 mumol.L-1 on KB cells. But no induction of differentiation of leukemic cell lines HL-60 and K562 was observed.
已发现有机锡化合物能明显抑制大鼠脑组织中磷脂/钙离子依赖性蛋白激酶（PKC）的活性以及体外肿瘤细胞系的增殖。结果表明，对PKC的作用与抗增殖和抗肿瘤活性之间存在相关性。结构-活性关系如下：（1）有机基团R决定生物活性；（2）卤素的电负性会影响活性。有机锡化合物通过其二价有机锡阳离子[SnR2]2+抑制肿瘤细胞，并抑制HL-60细胞周期的G1期向S期转变。[SnPh2F2]、[SnPh2(CysOS)].H2O和[SnPh2Cl2.phen(CH3)2]对PKC的IC50分别为25、15和20μmol·L-1，对HL-60细胞的IC50分别为0.5、4.0和0.3μmol·L-1，对BEL-7402细胞的IC50分别为2.7、9和1.5μmol·L-1，对KB细胞的IC50分别为2.2、15和5.0μmol·L-1。但未观察到白血病细胞系HL-60和K562的分化诱导现象。
