Novel Tumor-selective Anticancer Agents

描述(申请人提供)：最近，肿瘤细胞被发现选择性地积聚某些n-3脂肪酸，如顺-4，7，10，13，16，19-二十二碳六烯酸(DHA)。DHA-紫杉醇是DHA和紫杉醇的结合物，与游离紫杉醇相比，在实验动物和患者中具有显著提高疗效和减少副作用的作用。我们合成了一种专有的DHA-喜树碱结合物，在实验动物身上显示了显著的抗肿瘤活性。我们已经提交了关于这项发明的临时专利申请(US 60/401,195)。本研究的目的是合成新型的DHA喜树碱结合物，评价其体外和动物体内的抗肿瘤活性。预计新型DHA结合物将具有更高的抗肿瘤效果和更少的毒副作用。

DESCRIPTION (provided by applicant): Recently, tumor cells have been found to selectively accumulate certain n-3 fatty acids such as cis-4,7,10,13,16,19-docosahexenoic acid (DHA). DHA-paclitaxel, a conjugate of DHA and paclitaxel, has a greatly increased therapeutic efficacy and reduced side effects in both experimental animals and patients compared to free paclitaxel. We have synthesized a proprietary DHA-camptothecin conjugate that showed remarkable antitumor activity in experimental animals. We have filed a provisional patent application covering this invention (US 60/401,195). The objectives of this proposal are to synthesize novel DHA camptothecin conjugates, evaluate their antitumor activity in vitro and in experimental animals. It is expected that the novel DHA conjugates will have increased antitumor efficacies and reduced toxic side effects.