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

Otvagin, Vasilii F.; Nyuchev, Alexander V.; Kuzmina, Natalia S.; Grishin, Ivan D.; Gavryushin, Andrei E.; Romanenko, Yuliya V.; Koifman, Oscar I.; Belykh, Dmitrii V.; Peskova, Nina N.; Shilyagina, Natalia Yu; Balalaeva, Irina V. und Fedorov, Alexey Yu (2018): Synthesis and biological evaluation of new water-soluble photoactive chlorin conjugate for targeted delivery. In: European Journal of Medicinal Chemistry, Bd. 144: S. 740-750

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Chemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0223-5234
• Sprache: Englisch