Hall I H, Spielvogel B F, Sood A
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Anticancer Drugs. 1990 Dec;1(2):133-41. doi: 10.1097/00001813-199012000-00004.
Trimethylamine carboxyboranes including their esters and amides were shown to have antineoplastic activity in vivo against Ehrlich ascites carcinoma growth. The derivatization to the ester or amide did not necessarily improve activity. Cytotoxicity of the derivatives was observed against the growth of murine and human tumor cells. Selectivity was demonstrated by the boron derivatives in the human solid tumor screens. Almost all the compounds demonstrated cytotoxicity against single-cell suspension growths, eg Tmolt3, L1210, HeLa-S3. Selection of two compounds to examine their mode of action in L1210 lymphoid leukemia cells showed that the agents perferentially inhibited DNA synthesis followed by protein and RNA synthesis. The d(TTP) pools were markedly reduced because of inhibition of nucleotide kinase activity. The agents also inhibited regulatory enzymes in the de novo purine pathway and afforded DNA strand scission. These effects by the agents were probably additive to bring about tumor cell death.
三甲胺羧基硼烷及其酯类和酰胺类化合物在体内对艾氏腹水癌的生长显示出抗肿瘤活性。衍生为酯或酰胺并不一定会提高活性。观察到这些衍生物对鼠类和人类肿瘤细胞的生长具有细胞毒性。硼衍生物在人类实体瘤筛选中表现出选择性。几乎所有化合物对单细胞悬浮生长都具有细胞毒性，例如Tmolt3、L1210、HeLa-S3。选择两种化合物研究它们在L1210淋巴细胞白血病细胞中的作用方式，结果表明这些药剂优先抑制DNA合成，随后抑制蛋白质和RNA合成。由于核苷酸激酶活性受到抑制，d(TTP)池显著减少。这些药剂还抑制嘌呤从头合成途径中的调节酶，并导致DNA链断裂。这些药剂的这些作用可能相加导致肿瘤细胞死亡。
