Galatulas I, Andreani A, Rambaldi M, Bonazzi D, Bossa R
Anticancer Res. 1986 Jul-Aug;6(4):853-5.
The antimitotic properties associated with the bis (2-chloroethyl) amino group are well known, a number of compounds bearing this group being of therapeutic interest. The choice of a suitable supporting moiety for this group is important. Our experiments on a butyrophenone derivative, ketocaine, which possesses local anesthetic activity, showed that this drug is able to modify the oxygen consumption by tissues with prevailing anaerobic metabolism and to inhibit the mitotic activity of human lymphocytes in culture stimulated by phytohemagglutinin. These observations prompted us to prepare compounds by the general formula reported in Tables I and II. All compounds were tested in mice implanted i.p. with 10(6) Ehrlich ascites tumour cells. After 24 h the animals were treated with a single dose of the compound. The antitumor activity was correlated with: position (2, 4) and length (n = 0-2) of the chain with carbonyl group; presence (R' = H, ND2) and position (2, 4) of nitro group; monofunzional or bifunzional compound. Some of these show a potent antitumor activity.
与双（2-氯乙基）氨基相关的抗有丝分裂特性是众所周知的，许多含有该基团的化合物具有治疗意义。为该基团选择合适的支撑部分很重要。我们对具有局部麻醉活性的丁酰苯衍生物酮卡因进行的实验表明，这种药物能够改变主要进行无氧代谢的组织的耗氧量，并抑制植物血凝素刺激的培养人淋巴细胞的有丝分裂活性。这些观察结果促使我们制备表I和表II中所示通式的化合物。所有化合物均在腹腔注射10(6)个艾氏腹水瘤细胞的小鼠身上进行测试。24小时后，给动物单剂量注射化合物。抗肿瘤活性与以下因素相关：含羰基链的位置（2,4）和长度（n = 0-2）；硝基的存在（R' = H, ND2）和位置（2,4）；单官能或双官能化合物。其中一些显示出强大的抗肿瘤活性。
