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

Autor: Otvagin VF; Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation., Nyuchev AV; Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation., Kuzmina NS; Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation., Grishin ID; Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation., Gavryushin AE; Ludwig-Maximilians-Universität, Butenandtstrasse 5-13, 81377, Munich, Germany., Romanenko YV; Research Institute of Macroheterocycles, Ivanovo State University of Chemical Technology, 153000 Ivanovo, Russian Federation., Koifman OI; Research Institute of Macroheterocycles, Ivanovo State University of Chemical Technology, 153000 Ivanovo, Russian Federation., Belykh DV; Institute of Chemistry, Komi Scientific Center, Urals Branch of the Russian Academy of Sciences, 167982 Syktyvkar, Russian Federation., Peskova NN; Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation., Shilyagina NY; Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation., Balalaeva IV; Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation; Sechenov First Moscow State Medical University, Trubetskaya Str. 8-2, Moscow 119991, Russian Federation. Electronic address: irin-b@mail.ru., Fedorov AY; Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation. Electronic address: afnn@rambler.ru.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2018 Jan 20; Vol. 144, pp. 740-750. Date of Electronic Publication: 2017 Dec 19.
DOI: 10.1016/j.ejmech.2017.12.062
Abstrakt: 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 50dark /IC 50light ratio of 11-18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue.
(Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: