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目的维A酸(tretinoin)有良好的肿瘤抑制能力,但是它本身毒性大、水溶性差,限制了其在临床上的进一步应用。通过对其羧基修饰,可进一步提高其抗肿瘤能力、增加水溶性等。方法通过分析文献中具有抗肿瘤活性的维A酸及其衍生物的研究结果,总结维A酸衍生物改性的规律,为设计高活性、易临床应用的维A酸类抗肿瘤药物提供指导。结果与结论维A酸与羟基苯胺形成的酰胺或酯,或与其他药物分子形成的键合物,具有更高的抗肿瘤药效,其IC50在微摩尔水平,而维A酸与组蛋白去乙酰基酶抑制剂的键合物的IC50达到了纳摩尔水平,但这些衍生物的水溶性问题仍没有解决。通过键合负载的方法可有效提高其水溶性,并可提高药效。因此,键合负载维A酸可能是提高其药效和水溶性的有效方法。
The purpose of tretinoin has good tumor inhibition, but its own toxicity, poor water solubility, limiting its further clinical application. Through its carboxyl modification, can further improve its anti-tumor ability, increase water solubility and so on. Methods By analyzing the literature of the anti-tumor activity of retinoic acid and its derivatives of the results summarized Victoria retinoic acid derivative modification rules for the design of high activity, clinical application of Victoria A acid antitumor drugs to provide guidance . RESULTS AND CONCLUSION The amide or ester formed by retinoic acid and hydroxyaniline, or the bond formed with other drug molecules, has a higher anti-tumor efficacy with an IC50 at the micromolar level, whereas the ratio of retinoic acid to histone IC50s for acetylase inhibitor conjugates reach nanomolar levels, but the water-solubility problems of these derivatives remain unresolved. By bonding the load method can effectively improve its water-soluble, and can improve efficacy. Therefore, the binding of retinoic acid may be an effective method to improve its pharmacodynamics and water solubility.