Synthesis and biological evaluation of new water-soluble photoactive chlorin conjugate for targeted delivery

被引：43
作者：
Otvagin, Vasilii F. [1 ]
Nyuchev, Alexander V. [1 ]
Kuzmina, Natalia S. [1 ]
Grishin, Ivan D. [1 ]
Gavryushin, Andrei E. [2 ]
Romanenko, Yuliya V. [3 ]
Koifman, Oscar I. [3 ]
Belykh, Dmitrii V. [4 ]
Peskova, Nina N. [1 ]
Shilyagina, Natalia Yu [1 ]
Balalaeva, Irina V. [1 ,5 ]
Fedorov, Alexey Yu. [1 ]
机构：
[1] Lobachevsky State Univ Nizhny Novgorod, Gagarina Av 23, Nizhnii Novgorod 603950, Russia
[2] Ludwig Maximilians Univ Munchen, Butenandtstr 5-13, D-81377 Munich, Germany
[3] Ivanovo State Univ Chem Technol, Res Inst Macroheterocycles, Ivanovo 153000, Russia
[4] Russian Acad Sci, Inst Chem, Urals Branch, Komi Sci Ctr, Syktyvkar 167982, Russia
[5] Sechenov First Moscow State Med Univ, Trubetskaya Str 8-2, Moscow 119991, Russia
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 144卷
基金：
俄罗斯基础研究基金会;
关键词：
Chlorins; Conjugate; PDT; Targeted delivery; Water-solubility; Medicinal chemistry; ANTIMICROBIAL PHOTODYNAMIC THERAPY; FACTOR RECEPTOR EXPRESSION; DRUG-DELIVERY; IN-VIVO; LIPOSOMAL DOXORUBICIN; CHLOROPHYLL-A; CANCER; GROWTH; CELL; DERIVATIVES;
D O I：
10.1016/j.ejmech.2017.12.062
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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 IC50dark/IC50light ratio of 11-18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue. (C) 2017 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：740 / 750
页数：11
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