A cationic chalcogenoxanthylium photosensitizer effective in vitro in chemosensitive and multidrug-resistant cells

Holt, Jason J.; Gannon, Michael K.; Tombline, Gregory; McCarty, Taylor A.; Page, Phillip M.; Bright, Frank V.; Detty, Michael R.

doi:10.1016/j.bmc.2006.08.023

Cited by 22 publications

(33 citation statements)

References 36 publications

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“…Values for 5-Se , 6-Se , and 7-Se were compared to 19-Se (18) incorporating one julolidyl fragment and 20-Se incorporating one-half-julolidyl fragment.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Properties of Heavy Chalcogen Analogues of the Texas Reds and Related Rhodamines

et al. 2014

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Analogues of Texas red incorporating the heavy chalcogens S, Se, and Te atoms in the xanthylium core were prepared from the addition of aryl Grignard reagents to appropriate chalcogenoxanthone precursors. The xanthones were prepared via directed metalation of amide precursors, addition of dichalcogenide electrophiles, and electrophilic cyclization of the resulting chalcogenides with phosphorus oxychloride and triethylamine. The Texas red analogues incorporate two fused julolidine rings containing the rhodamine nitrogen atoms. Analogues containing two “half-julolidine” groups (a trimethyltetrahydroquinoline) and one julolidine and one “half-julolidine” were also prepared. The photophysics of the Texas red analogues were examined. The S-analogues were highly fluorescent, the Se-analogues generated single oxygen (1O2) efficiently upon irradiation, and the Te-analogues were easily oxidized to rhodamines with the telluroxide oxidation state. The tellurorhodamine telluroxides absorb at wavelengths ≥690 nm and emit with fluorescence maxima >720 nm. A mesityl-substituted tellurorhodamine derivative localized in the mitochondria of Colo-26 cells (a murine colon carcinoma cell line) and was oxidized in vitro to the fluorescent telluroxide.

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“…Values for 5-Se , 6-Se , and 7-Se were compared to 19-Se (18) incorporating one julolidyl fragment and 20-Se incorporating one-half-julolidyl fragment.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Properties of Heavy Chalcogen Analogues of the Texas Reds and Related Rhodamines

et al. 2014

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“…Oxidation of 18 to a carboxylic acid oxidation state was problematic as was observed for the oxidation of 9-formyljulolidine. 20 A modified Willgerodt-Kindler 18 reaction oxidized 18 to the thioamide 19 in 75-83% isolated yields using elemental sulfur and piperidine in refluxing DMF. 20 Amide 20 was formed from 19 using trifluoroacetic anhydride (TFAA) in isolated yields of > 90%.…”

Section: Resultsmentioning

confidence: 99%

“…16-18 Understanding the parameters that impact ATPase activity and binding affinity in rhodamine-like modulators of P-gp and the factors that influence the drug availability to the pump in the native membrane environment are critical for the development of more potent rhodamine-like inhibitors of P-gp that may have a dual application as photosensitizers for treatment of multidrug-resistant cells by PDT.…”

Section: Introductionmentioning

confidence: 99%

Thiorhodamines containing amide and thioamide functionality as inhibitors of the ATP-binding cassette drug transporter P-glycoprotein (ABCB1)

Orchard¹,

Schamerhorn²,

Calitree³

et al. 2012

Bioorganic & Medicinal Chemistry

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Twelve thiorhodamine derivatives have been examined for their ability to stimulate the ATPase activity of purified human P-glycoprotein (P-gp)-His10, to promote uptake of calcein AM and vinblastine into multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their rates of transport in monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells. The thiorhodamine derivatives have structural diversity from amide and thioamide functionality (N,N-diethyl and N-piperidyl) at the 5-position of a 2-thienyl substituent on the thiorhodamine core and from diversity at the 3-amino substituent with N,N-dimethylamino, fused azadecalin (julolidyl), and fused N-methylcyclohexylamine (half-julolidyl) substituents. The julolidyl and half-julolidyl derivatives were more effective inhibitors of P-gp than the dimethylamino analogues. Amide-containing derivatives were transported much more rapidly than thioamide-containing derivatives.

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“…Photodynamic therapy (PDT) is an effective modality against chemo- and radioresistant cancers due to its unique mechanisms of action, causing direct lipid and protein damage leading to mitochondrial-induced apoptosis that bypasses many mechanisms of classic multidrug-resistance 5–9 . This light-activated strategy makes use of a photosensitizing compound that is nontoxic in the dark but generates cytotoxic species when exposed to light of the appropriate wavelength.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous delivery of cytotoxic and biologic therapeutics using nanophotoactivatable liposomes enhances treatment efficacy in a mouse model of pancreatic cancer

Tangutoori

Spring

Mai

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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A lack of intracellular delivery systems has limited the use of biologics such as monoclonal antibodies (mAb) that abrogate molecular signaling pathways activated to promote escape from cancer treatment. We hypothesized that intracellular co-delivery of the photocytotoxic chromophore benzoporphyrin derivative monoacid A (BPD) and the anti-VEGF mAb bevacizumab in a nanophotoactivatable liposome (nanoPAL) might enhance the efficacy of photodynamic therapy (PDT) combined with suppression of VEGF-mediated signaling pathways. As a proof-of-concept we found that nanoPAL-PDT induced enhanced extra- and intracellular bevacizumab delivery and enhanced acute cytotoxicity in vitro. In an in vivo subcutaneous mouse model of pancreatic ductal adenocarcinoma, nanoPAL-PDT achieved significantly enhanced tumor reduction. We attribute this to the optimal incorporation of insoluble BPD into the lipid bilayer, enhancing photocytotoxicity, and the simultaneous spatiotemporal delivery of bevacizumab, ensuring efficient neutralization of the rapid but transient burst of VEGF following PDT.

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A cationic chalcogenoxanthylium photosensitizer effective in vitro in chemosensitive and multidrug-resistant cells

Cited by 22 publications

References 36 publications

Synthesis and Properties of Heavy Chalcogen Analogues of the Texas Reds and Related Rhodamines

Synthesis and Properties of Heavy Chalcogen Analogues of the Texas Reds and Related Rhodamines

Thiorhodamines containing amide and thioamide functionality as inhibitors of the ATP-binding cassette drug transporter P-glycoprotein (ABCB1)

Simultaneous delivery of cytotoxic and biologic therapeutics using nanophotoactivatable liposomes enhances treatment efficacy in a mouse model of pancreatic cancer

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