摘要
有机锡（ＩＶ）化合物能明显地抑制大鼠脑组织中ＰＫＣ活性和肿瘤细胞增殖，且两者之间存在着相关性。抗肿瘤活性的构效关系是：（１）有机基团Ｒ决定整个化合物的生物活性，Ｐｈ＞Ｅｔ＞ｎ－Ｂｕ；（２）卤素的电负性影响化合物活性的大小。抗肿瘤活性可能通过［ＳｎＲ２］２＋实现。并能部分地阻断ＨＬ－６０细胞周期中的Ｇ１期向ｓ期的移行。［ＳｎＰｈ２Ｆ２］，［ＳｎＰｈ２（ＣｙｓＯＳ）］ＨＯ２和［ＳｎＰｈ２Ｃｌ２·ｐｈｅｎ（ＣＨ３）２］对ＰＫＣ的ＩＣ５０值分别为２５，１５和２０μｍｏｌ·Ｌ－１，对ＨＬ－６０细胞的ＩＣ５０值分别为０．５，４．０和０．３μｍｏｌ·Ｌ－１。但它们无诱导分化ＨＬ－６０和Ｋ５６２细胞的作用。
Organotin compounds were found to obviously inhibit the activity of
phospholipid/Ca2+-dependent protein kinase(PKC)in rat brain tissue
and the proliferation of tumor cell lines invitro. The results showed
that a correlation exists between the effects on PKC and
anti-proliferativeand antitumor activities.The structure-activity
relationship was shown to be as follows:(1)R,theorganic group
determines the biological activity;(2) electronegativity of the
halogen can affect theactivity. The organotin compounds inhibit tumor
cells by its [SnR2]2+, and inhibit G1→S phases ofHL-60 cell cycle.
The IC50 of [SnPh2F2], [SnPh2(CysOS)]·H2O and[SnPh2Cl2·
phen(CH3)2]are respectively 25, 15 and 20μmol·L-1 on PKC,0.5,4. 0
and 0.3μmol·L-1 on HL-60 cells,2.7, 9 and l.5 μmol·L-1 on
BEL-7402 cells,2.2, 15 and 5.0μmol·L-1 on KB cells. But noinduction
of differentiation of leukemic cell lines HL-60 and K562 was
observed.
出处
《药学学报》
CAS
CSCD
北大核心
1994年第6期406-411,共6页
Acta Pharmaceutica Sinica
基金
天然药物及仿生药物国家重点实验室和国家自然科学基金
关键词
有机锡化合物
蛋白激酶
抗肿瘤作用
Organotin compounds
Protein kinase C
Antitumor
action
Differentiation The work was supported by Research Foundation
of Mational Laboratory of Natural and Biomimetic Drugs.New address:
Mational Laboratory of Natural and Biomimetic Drugs,Beijing Medic
