Development of a palmitic acid-derived anticancer drug for the treatment of human colon cancer

本研究的最终目标是开发一种脂肪酸衍生的抗癌药物用于治疗人结肠癌。我们决定使用天然脂肪酸癸烯酸和棕榈酸作为先导化合物。通过定量构效关系（QSAR）分析，我们发现棕榈酸衍生物的抗肿瘤活性与其16个碳原子的饱和脂肪族尾链和C-1位的哌啶环侧链有关。化合物代码903被确定为最有效的抗癌剂，其对正常上皮细胞的毒性较小。在裸鼠异种移植模型中，该药剂抑制植入的肿瘤细胞的生长。我们估计ip治疗的有效剂量为0.025-0.05 mg/kg。根据pKa和cLogD值，认为化合物代码903从胃肠道吸收。药物代码903可能是一个有前途的先导化合物，用于治疗结肠癌和其他实体瘤，因为它的广泛的癌症杀伤活性和显着的肿瘤特异性。

The final goal of the present study was to develop a fatty acid-derived anticancer drug for the treatment of human colon cancer. We decided to use the natural fatty acid decenoic acid and palmitic acid as lead compounds. Using quantitative structure activity relationship (QSAR) analysis, we found that a saturated aliphatic tail of 16 carbon atoms and a side chain at the C-1 position composed of piperidine rings markedly contribute to the in vitro anticancer effects of the palmitic acid derivatives. Compound code 903 was determined to be the most effective anticancer agent, which was less toxic to normal epithelial cells. In a nude mouse xenograft model, this agent inhibited the growth of implanted tumor cells. We estimated that the effective dose of ip treatment would be 0.025-0.05 mg/kg. Compound code 903 was thought to be absorbed from gastrointestinal tract by values of pKa and cLogD. The drug code 903 may be a promising lead compound for the treatment of colon cancer and other solid tumors because of its broad cancer killing activity and significant tumor specificity.