Department of Chemistry, University of Modena and Reggio Emilia, Via Campi 183, 41125 Modena, Italy.
J Med Chem. 2011 Dec 8;54(23):8066-77. doi: 10.1021/jm200872q. Epub 2011 Nov 11.
New curcumin analogues (ester and acid series) were synthesized with the aim to improve the chemical stability in physiological conditions and potential anticancer activity. Cytotoxicity against different tumorigenic cell lines (human ovarian carcinoma cells -2008, A2780, C13*, and A2780/CP, and human colon carcinoma cells HCT116 and LoVo) was tested to evaluate cellular specificity and activity. Physico-chemical properties such as acidity, lipophilicity, kinetic stability, and free radical scavenging activity were investigated to shed light on the structure-activity relationship and provide new attractive candidates for drug development. Most of ester derivatives show IC(50) values lower than curcumin and exhibit selectivity against colon carcinoma cells. Especially they are extremely active after 24 h exposure showing enhanced inhibitory effect on cell viability. The best performances of ester curcuminoids could be ascribed to their high lipophilicity that favors a greater and faster cellular uptake overcoming their apparently higher instability in physiological condition.
新型姜黄素类似物（酯和酸系列）被合成，目的是提高在生理条件下的化学稳定性和潜在的抗癌活性。用不同的致瘤细胞系（人卵巢癌细胞 -2008、A2780、C13* 和 A2780/CP，以及人结肠癌细胞 HCT116 和 LoVo）测试了细胞毒性，以评估细胞特异性和活性。研究了物理化学性质，如酸度、亲脂性、动力学稳定性和自由基清除活性，以阐明构效关系并提供新的有吸引力的药物开发候选物。大多数酯衍生物的 IC(50) 值低于姜黄素，并且对结肠癌细胞具有选择性。特别是它们在 24 小时暴露后表现出极高的活性，对细胞活力的抑制作用更强。酯类姜黄素类化合物的最佳性能可归因于它们的高亲脂性，有利于更大和更快的细胞摄取，从而克服了它们在生理条件下明显更高的不稳定性。
