Department of Chemistry, Middle East Technical University (METU), 06800, Ankara, Turkey.
Department of Chemistry, Koc University, 34450, Istanbul, Turkey.
ChemMedChem. 2019 Nov 20;14(22):1879-1886. doi: 10.1002/cmdc.201900380. Epub 2019 Nov 5.
Two red-absorbing, water-soluble and mitochondria (MT)-targeting selenophene-substituted BODIPY-based photosensitizers (PSs) were realized (BOD-Se, BOD-Se-I), and their potential as photodynamic therapy (PDT) agents were evaluated. BOD-Se-I showed higher O generation yield thanks to the enhanced heavy-atom effect, and this derivative was further tested in detail in cell culture studies under both normoxic and hypoxic conditions. BOD-Se-I not only effectively functioned under hypoxic conditions, but also showed highly selective photocytotoxicity towards cancer cells. The selectivity is believed to arise from differences in mitochondrial membrane potentials of healthy and cancerous cells. To the best of our knowledge, this marks the first example of a MT-targeted BODIPY PS that functions under hypoxic conditions. Remarkably, thanks to the design strategy, all these properties where realized by a compound that was synthesized in only five steps with 32 % overall yield. Hence, this material holds great promise for the realization of next-generation PDT drugs for the treatment of hypoxic solid tumors.
两种红色吸收、水溶性和靶向线粒体 (MT) 的硒吩取代 BODIPY 基光敏剂 (PS) 被实现 (BOD-Se、BOD-Se-I)，并评估了它们作为光动力疗法 (PDT) 药物的潜力。BOD-Se-I 由于增强的重原子效应而显示出更高的 O 生成产率，并且该衍生物在常氧和缺氧条件下的细胞培养研究中进一步进行了详细测试。BOD-Se-I 不仅在缺氧条件下有效发挥作用，而且对癌细胞具有高度选择性的光细胞毒性。这种选择性被认为源于健康细胞和癌细胞中线粒体膜电位的差异。据我们所知，这是首例在缺氧条件下发挥作用的靶向 MT 的 BODIPY PS 的例子。值得注意的是，由于设计策略，所有这些特性都是通过一种仅用五步合成、总收率为 32%的化合物实现的。因此，这种材料为实现用于治疗缺氧实体瘤的下一代 PDT 药物提供了巨大的前景。
