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

Date

2019-11-05

Author

Karaman, Osman
Almammadov, Toghrul
Gedik, M. Emre
GÜNAYDIN, GÜRCAN
Kolemen, Safacan
Günbaş, Emrullah Görkem

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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 O-1(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.

Subject Keywords

General Pharmacology, Toxicology and Pharmaceutics, Organic Chemistry, Molecular Medicine

URI

https://hdl.handle.net/11511/43010

Journal

CHEMMEDCHEM

DOI

https://doi.org/10.1002/cmdc.201900380

Collections

Department of Chemistry, Article

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Citation Formats

O. Karaman, T. Almammadov, M. E. Gedik, G. GÜNAYDIN, S. Kolemen, and E. G. Günbaş, “Mitochondria-Targeting Selenophene-Modified BODIPY-Based Photosensitizers for the Treatment of Hypoxic Cancer Cells,” CHEMMEDCHEM, pp. 1879–1886, 2019, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/43010.