Takasaki M, Konoshima T, Kozuka M, Yoneyama K, Yoshida S, Tokuda H, Nishino H, Iwashima A
Kyoto Pharmaceutical University, Kyoto, Japan.
Biol Pharm Bull. 1995 Feb;18(2):288-94. doi: 10.1248/bpb.18.288.
One hundred and fifteen synthesized mono, di, and trihydroxybenzamide and thiobenzamide derivatives having structures related to euglobals were examined for their inhibitory effects on Epstein-Barr virus (EBV) activation by 12-O-tetradecanoylphorbol-13-acetate (TPA) as a primary screening test for anti-tumor-promoters. In general, 3-acyl-2,4,6-trihydroxybenzamide and 3-acyl-2,4,6-trihydroxythiobenzamide derivatives exhibited strong or moderate activities, and the latter compounds were less cytotoxic than the former. Meanwhile, little or no activity was observed with mono and dihydroxybenzamide and dihydroxythiobenzamide derivatives. Structural requirements for the activities of these compounds have been discussed in detail. Among the above compounds, compounds 36 and 73, which were significantly active on the inhibition of EBV activation, were investigated using a two-stage mouse skin carcinogenesis test induced by 7,12-dimethylbenz[a]anthracene (DMBA) and TPA. The results of the in vivo test showed that both compounds have a stronger inhibitory effect than that of the well-known anti-tumor-promoter, glycyrrhetic acid. These results suggested that the two compounds might be valuable as anti-tumor-promoters in chemical carcinogenesis.
对115种合成的具有与优球蛋白相关结构的单羟基、二羟基和三羟基苯甲酰胺及硫代苯甲酰胺衍生物进行了检测，以考察它们对由12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）诱导的爱泼斯坦 - 巴尔病毒（EBV）激活的抑制作用，作为抗肿瘤促进剂的初步筛选试验。一般来说，3 - 酰基 - 2,4,6 - 三羟基苯甲酰胺和3 - 酰基 - 2,4,6 - 三羟基硫代苯甲酰胺衍生物表现出强或中等活性，且后一类化合物的细胞毒性比前一类小。同时，单羟基和二羟基苯甲酰胺及二羟基硫代苯甲酰胺衍生物几乎没有活性或没有活性。已详细讨论了这些化合物活性的结构要求。在上述化合物中，对抑制EBV激活有显著活性的化合物36和73，使用由7,12 - 二甲基苯并[a]蒽（DMBA）和TPA诱导的两阶段小鼠皮肤致癌试验进行了研究。体内试验结果表明，这两种化合物的抑制作用均强于著名的抗肿瘤促进剂甘草次酸。这些结果表明，这两种化合物在化学致癌过程中作为抗肿瘤促进剂可能具有重要价值。
