Srdanović Sonja, Gao Ying-Hua, Chen Dan-Ye, Yan Yi-Jia, Margetić Davor, Chen Zhi-Long
Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000, Croatia.
Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai 201620, China.
Bioorg Med Chem Lett. 2018 Jun 1;28(10):1785-1791. doi: 10.1016/j.bmcl.2018.04.025. Epub 2018 Apr 12.
A novel 13-pyridine substituted chlorin e derivative (Chlorin A) was synthesized. It has characteristic long wavelength absorption at 664 nm and the emission wavelength at 667 nm. The generation rate of singlet oxygen of this compound is higher than Temoporfin. In vitro, Chlorin A showed higher phototoxicity against the human esophageal cancer cells than Temoporfin while with lower dark-toxicity. Its accumulation effect in mitochondria, lysosomes and endoplasmic reticulum was traced in subcellular localization tests. In flow cytometry obvious apoptosis cells were observed after 2 h irradiation. Significant in vivo photodynamic anti-tumor efficacy was also exhibited on mice bearing esophageal cancer. So Chlorin A could be suggested as a promising anti-tumor drug candidate in photodynamic therapy.
合成了一种新型的13-吡啶取代二氢卟吩e衍生物（二氢卟吩A）。它在664nm处有特征性的长波长吸收，发射波长为667nm。该化合物的单线态氧生成率高于替莫泊芬。在体外，二氢卟吩A对人食管癌细胞的光毒性高于替莫泊芬，而暗毒性较低。在亚细胞定位试验中追踪了其在线粒体、溶酶体和内质网中的积累效应。在流式细胞术中，照射2小时后观察到明显的凋亡细胞。对荷食管癌小鼠也显示出显著的体内光动力抗肿瘤疗效。因此，二氢卟吩A有望成为光动力治疗中有前景的抗肿瘤药物候选物。
