Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation.
Ludwig-Maximilians-Universität, Butenandtstrasse 5-13, 81377, Munich, Germany.
Eur J Med Chem. 2018 Jan 20;144:740-750. doi: 10.1016/j.ejmech.2017.12.062. Epub 2017 Dec 19.
A new water-soluble conjugate, consisting of a chlorin-based photosensitizing part, and a 4-arylaminoquinazoline moiety with high potential affinity to an epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), suitable for photodynamic therapy (PDT), was synthesized starting from methylpheophorbide-a in seven steps. An increased accumulation of this compound in A431 cells with high level of EGFR expression, in comparison with CHO and HeLa cells with low EGFR expression was observed. The prepared conjugate exhibits dark and photoinduced cytotoxicity at micromolar concentrations with IC/IC ratio of 11-18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue.
一种新型的水溶性偶联物，由基于叶绿素的光敏部分和具有高表皮生长因子受体（EGFR）和血管内皮生长因子受体（VEGFR）亲和力的 4-芳基氨基喹唑啉部分组成，适用于光动力疗法（PDT），是从甲基 pheophorbide-a 经七步合成的。与低 EGFR 表达的 CHO 和 HeLa 细胞相比，该化合物在高 EGFR 表达的 A431 细胞中的积累增加。该偶联物在微摩尔浓度下表现出暗毒性和光诱导细胞毒性，IC/IC 比值为 11-18。在荷瘤小鼠中，该偶联物优先积聚在肿瘤组织中。
