In Vitro and In Vivo Photocytotoxicity of Boron Dipyrromethene Derivatives for Photodynamic Therapy
In Vitro and In Vivo Photocytotoxicity of Boron Dipyrromethene Derivatives for Photodynamic Therapy
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DOI：
10.1021/jm901823u
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发表时间：
2010-04-08
影响因子：
7.3
通讯作者：
Lee, Hong Boon
中科院分区：
文献类型：
--
作者：
Lim, Siang Hui;Thivierge, Cliferson;Lee, Hong Boon
为了了解取代模式对硼二吡咯亚甲基（BODIPY）的光敏化能力的影响，研究了两种结构变化，即研究各种碘化衍生物的有效性以最大化“重原子效应”或关注4-吡咯位置处的扩展共轭效应以使其活化波长红移。在4-吡咯位置具有缀合的化合物比母体未缀合的化合物具有更少的光细胞毒性，而具有碘化BODIPY核心的那些化合物比在中间位具有碘芳基的化合物具有更好的光细胞毒性。衍生物的效力通常与它们的单线态氧生成水平良好相关。化合物5对HSC-2细胞的进一步研究显示几乎仅定位于线粒体，诱导G（2）/M期细胞周期阻滞，并开始凋亡。化合物5还广泛地封闭鸡绒毛尿囊膜的脉管系统。碘化BODIPY结构如化合物5可能具有作为癌症的新光动力治疗剂的潜力。
To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrromethene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives to maximize the "heavy atom effect" or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated compound, while those with an iodinated BODIPY core presented better photocytotoxicity than compounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G(2)/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY structures such as compound 5 may have potential as new photodynamic therapy agents for cancer.