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Effects of nine retinoids on carinogenesis of the forestomach in mice were studied. RⅠ, RⅡ, RⅢ, RⅥ, and RⅧ showed significaut inhibitory effect. RⅠ[N-(4-ethoxycarbophenyl) Retinanide] appeared to be the most effective, reproducible and has not been reported in the literature. No toxic effect was observed with therapeutic dose of RⅠ, and no sign of hypervitaminosis A was noticed with dosage as high as 6 times the therapeutic dose. However hypervitamnosis A was induced with retinoic acid at the some...

Effects of nine retinoids on carinogenesis of the forestomach in mice were studied. RⅠ, RⅡ, RⅢ, RⅥ, and RⅧ showed significaut inhibitory effect. RⅠ[N-(4-ethoxycarbophenyl) Retinanide] appeared to be the most effective, reproducible and has not been reported in the literature. No toxic effect was observed with therapeutic dose of RⅠ, and no sign of hypervitaminosis A was noticed with dosage as high as 6 times the therapeutic dose. However hypervitamnosis A was induced with retinoic acid at the some dose. The toxiciity of RⅡ appeared to the much less than that of retinoic acid.Autoradiography using H~3-thymidine showed marked inhibitory effect of RⅡ on DNA synthesis in the forestomach epithelium of mice.

本文报道9种维生素甲酸衍生物对小鼠前胃上皮癌变的影响,其中有抑制作用的有:RⅠ、RⅡ、RⅢ、RⅥ及RⅧ,尤以RⅠ[N-(4-乙氧羰基苯基)维甲酰胺][N-(4-Ethoxycarbophenyl)Retinamide]抑制上皮癌变作用明显,并可重复,文献上未见报道。RⅠ在治疗剂量下(1.1×10~(-4)M/kg)未出现毒性,六倍于治疗剂量,亦未见高维生素甲症,而相应剂量的维甲酸,引起明显的高维生素甲症,RⅠ毒性远较维甲酸小。用氚—胸腺嘧啶核苷放射自显影方法,观察到RⅡ对小鼠前胃上皮细胞DNA合成有明显的抑制作用。

In search of agents for tumor prevention, attempt to improve the biological activity of the parent compound, retinoic acid, was carried out by preparing its esters and amides through which the physical and chemical properties and pharmacodynamics might be changed. Twenty-seven retinoic acid esters and retinamides were prepared by treating the corresponding amine and alcohol with retinyl chloride which was obtained from retinoic acid and phosphorous trichloride. Animal tests...

In search of agents for tumor prevention, attempt to improve the biological activity of the parent compound, retinoic acid, was carried out by preparing its esters and amides through which the physical and chemical properties and pharmacodynamics might be changed. Twenty-seven retinoic acid esters and retinamides were prepared by treating the corresponding amine and alcohol with retinyl chloride which was obtained from retinoic acid and phosphorous trichloride. Animal tests of part of the compounds reported in this paper showed that some of them exhibited preventive activity against carcinogenic action of nitrososarcosine among which compound (1), N-(4-ethoxycarbophenyl) retinamide showed higher activity and lower toxicity.

为寻找防癌药物,从改变维甲酸的结构、物化性质,以改变在体内的运转、分布和生物活性,达到提高疗效,降低毒性的目的,而合成了27个维甲酸酯和酰胺衍生物。部分化合物已进行预防致癌实验。结果证明,有些化合物有效,其中维甲酰(4-乙氧羰基苯胺)(1)的效果较好,毒性低,可能是一个有希望的防癌化合物。

Using chick embryo metatarsal skin organ culture, the biological activities of 8 kinds of new retinoids were tested. The results of investigation of 684 samples were reported. RI ( N-4-ethoxycarbophenyl-retinamide ) was a retinoid derivative, which showed a higher inhibitory rate on carcino-genesis in vivo and a marked inhibition on keratosis in vitro. It showed that this method was highly sensitive, with high reproducibility and easy to perform. Comparative studies on inhibitory effects of RI, retinoic...

Using chick embryo metatarsal skin organ culture, the biological activities of 8 kinds of new retinoids were tested. The results of investigation of 684 samples were reported. RI ( N-4-ethoxycarbophenyl-retinamide ) was a retinoid derivative, which showed a higher inhibitory rate on carcino-genesis in vivo and a marked inhibition on keratosis in vitro. It showed that this method was highly sensitive, with high reproducibility and easy to perform. Comparative studies on inhibitory effects of RI, retinoic acid, and natural retinol showed that the effect of RI was higher than retinol and lower than retinoic acid. Photo-degradation of retinoids was different. After exposing to light for 1 hour the biological activity of RI decreased, but not that of RII and RVIII.

用13天龄鸡胚脚掌皮肤体外培养,测定8种新维甲酸衍生物的活性发现。RⅠ(N-(4-乙氧羰基苯基)维甲酰胺)在体内对上皮癌变的抑制率最高,在体外抑制角化率亦最强。本方法简便、灵敏、重复性强,是一种较好的初筛方法。RⅠ抑制角化率的作用较天然维甲醇高,而低于维甲酸。RⅠ光解后活性降低。RⅡ和RⅧ光照1小时不受影响。

 
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