Chegaev Konstantin, Fraix Aurore, Gazzano Elena, Abd-Ellatef Gamal Eldein F, Blangetti Marco, Rolando Barbara, Conoci Sabrina, Riganti Chiara, Fruttero Roberta, Gasco Alberto, Sortino Salvatore
Department of Drug Science and Technology, University of Torino , I-10125 Torino, Italy.
Laboratory of Photochemistry, Department of Drug Sciences, University of Catania , I-95125 Catania, Italy.
ACS Med Chem Lett. 2017 Jan 30;8(3):361-365. doi: 10.1021/acsmedchemlett.7b00016. eCollection 2017 Mar 9.
Nitric oxide (NO) release from a suitable NO photodonor () can be fine-tuned by visible light stimuli at doses that are not toxic to cells but that inhibit several efflux pumps; these are mainly responsible for the multidrug resistance of the anticancer agent doxorubicin (). The strategy may thus increase toxicity against resistant cancer cells. Moreover, a novel molecular hybrid covalently joining and showed similar increased toxicity toward resistant cancer cells and, in addition, lower cardiotoxicity than . This opens new and underexplored approaches to overcoming the main therapeutic drawbacks of this chemotherapeutic based on light-controlled release of NO.
通过合适的一氧化氮光供体释放一氧化氮可通过可见光刺激进行微调，其剂量对细胞无毒，但会抑制几种外排泵；这些外排泵主要导致抗癌药物阿霉素的多药耐药性。因此，该策略可能会增加对耐药癌细胞的毒性。此外，一种将[具体物质1]和[具体物质2]共价连接的新型分子杂化物对耐药癌细胞也表现出类似的毒性增加，并且与[对比物质]相比，心脏毒性更低。这为克服基于一氧化氮光控释放的这种化疗方法的主要治疗缺陷开辟了新的、尚未充分探索的途径。
