Dipartimento di Specialità Medico Chirurgiche e Sanità Pubblica, Sezione di Epidemiologia Molecolare e Igiene Ambientale, Università di Perugia, Via del Giochetto, 06126 Perugia, Italy.
Eur J Pharm Sci. 2013 Mar 12;48(4-5):790-8. doi: 10.1016/j.ejps.2012.12.028. Epub 2013 Jan 9.
Thio derivatives of hydroxytyrosol containing thiol, thioacetate and disulfide functionalities were synthesized from natural hydroxytyrosol (3,4-DHPEA) via 3,4-dihydroxyphenethyl halides. These compounds, containing the combination of catechol moiety and divalent sulfur functions, were tested for the pro-apoptotic and anti-proliferative activities on both parental HL60 and multi-drug resistant HL60R cells. It was found that all synthesized compounds were more effective than 3,4-DHPEA in inducing apoptosis on HL60R cells, and that the hydroxytyrosol disulfide was the most active pro-apoptotic and anti-proliferative compound on both HL60 and HL60R cells. Different from 3,4-DHPEA, all thio derivatives of hydroxytyrosol induced apoptosis by a mechanism not involving the release of H(2)O(2) in the culture medium. The data on HL60R cells suggest that these compounds could be able to reverse the resistance toward the most common drugs in cancer therapy.
硫醇、硫代乙酸酯和二硫化物功能的羟基酪醇硫衍生物是通过 3,4-二羟基苯乙烷基卤化物从天然羟基酪醇（3,4-DHPEA）合成的。这些化合物含有儿茶酚部分和二价硫功能的组合，在亲本 HL60 和多药耐药 HL60R 细胞上测试了它们的促凋亡和抗增殖活性。结果发现，所有合成的化合物在诱导 HL60R 细胞凋亡方面都比 3,4-DHPEA 更有效，而羟基酪醇二硫化物是对 HL60 和 HL60R 细胞具有最强促凋亡和抗增殖活性的化合物。与 3,4-DHPEA 不同，所有羟基酪醇的硫代衍生物诱导凋亡的机制不涉及培养基中 H2O2 的释放。HL60R 细胞的数据表明，这些化合物能够逆转癌症治疗中最常用药物的耐药性。
