Mitochondria-Targeting Selenophene-Modified BODIPY-Based Photosensitizers for the Treatment of Hypoxic Cancer Cells.

Autor: Karaman O; Department of Chemistry, Middle East Technical University (METU), 06800, Ankara, Turkey., Almammadov T; Department of Chemistry, Koc University, 34450, Istanbul, Turkey., Emre Gedik M; Department of Basic Oncology, Hacettepe University, 06100, Ankara, Turkey., Gunaydin G; Department of Basic Oncology, Hacettepe University, 06100, Ankara, Turkey., Kolemen S; Department of Chemistry, Koc University, 34450, Istanbul, Turkey.; Koc University (KU), Surface Science and Technology Center (KUYTAM), 34450, Istanbul, Turkey., Gunbas G; Department of Chemistry, Middle East Technical University (METU), 06800, Ankara, Turkey.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2019 Nov 20; Vol. 14 (22), pp. 1879-1886. Date of Electronic Publication: 2019 Nov 05.
DOI: 10.1002/cmdc.201900380
Abstrakt: 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 1 O 2 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.
(© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
Externí odkaz: