Chegaev Konstantin, Riganti Chiara, Lazzarato Loretta, Rolando Barbara, Guglielmo Stefano, Campia Ivana, Fruttero Roberta, Bosia Amalia, Gasco Alberto
Department of Drug Science and Technology, University of Turin , Via Pietro Giuria 9, 10125 Torino, Italy.
Department of Genetics, Biology and Biochemistry, Turin School of Medicine, University of Turin , via Santena 5/bis, 10126 Torino, Italy.
ACS Med Chem Lett. 2011 Apr 4;2(7):494-7. doi: 10.1021/ml100302t. eCollection 2011 Jul 14.
Products 4 and 5, obtained by conjugation of doxorubicin with nitric oxide (NO) donor nitrooxy and phenylsulfonyl furoxan moieties, respectively, accumulate in doxorubicin-resistant human colon cancer cells (HT29-dx), inducing high cytotoxicity. This behavior parallels the ability of the compounds to generate NO, detected as nitrite, in these cells. Preliminary immunoblotting studies suggest that the mechanism that underlies the cytotoxic effect could involve inhibition of cellular drug efflux due to nitration of tyrosine residues of the MRP3 protein pump.
分别通过将阿霉素与一氧化氮（NO）供体硝氧基和苯磺酰基呋咱部分缀合得到的产物4和5，在耐阿霉素的人结肠癌细胞（HT29-dx）中积累，诱导高细胞毒性。这种行为与这些化合物在这些细胞中产生作为亚硝酸盐检测到的NO的能力相似。初步免疫印迹研究表明，细胞毒性作用背后的机制可能涉及由于MRP3蛋白泵酪氨酸残基的硝化而抑制细胞药物外排。
