Selenorhodamine Photosensitizers for Photodynamic Therapy of P‑Glycoprotein-Expressing Cancer Cells

We examined a series of selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenorhodamine core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp) expressing cells. These compounds were examined...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2014-10, Vol.57 (20), p.8622-8634
Main Authors: Hill, Jacqueline E, Linder, Michelle K, Davies, Kellie S, Sawada, Geri A, Morgan, Janet, Ohulchanskyy, Tymish Y, Detty, Michael R
Format: Article
Language:English
Subjects:
Animals
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Cell Line, Tumor - drug effects
Cell Line, Tumor - metabolism
Chemistry Techniques, Synthetic
Dogs
Doxorubicin - pharmacology
Drug Screening Assays, Antitumor - methods
Humans
Madin Darby Canine Kidney Cells - drug effects
Mice
Organoselenium Compounds - chemical synthesis
Organoselenium Compounds - chemistry
Organoselenium Compounds - pharmacology
Photochemotherapy - methods
Photosensitizing Agents - chemical synthesis
Photosensitizing Agents - chemistry
Photosensitizing Agents - pharmacology
Rhodamines - pharmacokinetics
Singlet Oxygen - metabolism
Spectrometry, Fluorescence
Toxicity Tests
Verapamil - pharmacology
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Summary:We examined a series of selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenorhodamine core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp) expressing cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their uptake into Colo-26 cells in the absence or presence of verapamil, for their dark and phototoxicity toward Colo-26 cells, for their rates of transport in monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their colocalization with mitochondrial specific agents in Colo-26 cells. Thioamide derivatives 16b and 18b were more effective photosensitizers than amide derivatives 15b and 17b. Selenorhodamine thioamides 16b and 18b were useful in a combination therapy to treat Colo-26 cells in vitro: a synergistic therapeutic effect was observed when Colo-26 cells were exposed to PDT and treatment with the cancer drug doxorubicin.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm501259v