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

Orchard, Alexandra; Schamerhorn, Gregory A.; Calitree, Brandon D.; Loo, Tip W.; Bartlett, M. Claire; Clarke, David M.; Detty, Michael R.

doi:10.1016/j.bmc.2012.05.075

Cited by 11 publications

(44 citation statements)

References 44 publications

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“…In the absence of VER, the uptake of thioamide 6 is 3-fold greater (p <0.015) than the uptake of amide 5 and is consistent with results we have observed in other rhodamine amide/thioamide pairs. 12,14 The thioamide is likely transported more slowly than the corresponding amide in the efflux direction. Thus, 6 possibly occupies the pump for longer periods of time and allows for an increase in intracellular accumulation compared to the analogous amide derivative.…”

Section: Discussion Of Biological Resultsmentioning

confidence: 99%

Selenorhodamine photosensitizers with the Texas-red core for photodynamic therapy of cancer cells

Kryman¹,

Davies²,

Linder³

et al. 2015

Bioorganic & Medicinal Chemistry

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Section: Discussion Of Biological Resultsmentioning

confidence: 99%

Selenorhodamine photosensitizers with the Texas-red core for photodynamic therapy of cancer cells

Kryman¹,

Davies²,

Linder³

et al. 2015

Bioorganic & Medicinal Chemistry

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“…P-gp (also known as MDR1 or ABCB1) is a member of the ATP-binding cassette (ABC) superfamily and was the first efflux protein identified. Recently, simple substitutions in a series of chalcogenorosamine/rhodamine structures have been shown to create molecules that possess a high affinity for P-gp and are either highly stimulating or inhibiting for ATPase activity (27, 28). Based on this observation, we developed a small library of 24 photosensitive agents that modulate P-gp.…”

Section: Resultsmentioning

confidence: 99%

Targeting T Cell Bioenergetics by Modulating P-Glycoprotein Selectively Depletes Alloreactive T Cells To Prevent Graft-versus-Host Disease

McIver

Grayson

Coe

et al. 2016

The Journal of Immunology

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T lymphocytes play a central role in many human immunologic disorders including autoimmune and alloimmune diseases. In hematopoietic stem cell transplant, acute graft-versus-host-disease (GVHD) is caused by an attack on the recipient’s tissues from donor allogeneic T cells. Selectively depleting GVHD-causing cells prior to transplant may prevent GVHD. In this report we have evaluated 24 chalcogenorhodamine photosensitizers for their ability to selectively deplete reactive T lymphocytes, and identified the photosensitizer 2-Se-Cl that accumulates in stimulated T cells in proportion to oxidative phosphorylation (OXPHOS). The photosensitizer is also a potent stimulator of P-glycoprotein (P-pg). Enhanced P-gp activity promotes the efficient removal of photosensitizer not sequestered in mitochondria, and protects resting lymphocytes essential for antipathogen and antitumor responses. To evaluate the selective depletion of alloimmune responses, donor C57BL/6 splenocytes were cocultured for 5 days with irradiated Balb/c splenocytes, and then photodepleted (PD). PD-treated splenocytes were then infused into lethally irradiated BALB/c (same-party) or C3H/HeJ (third-party) mice. Same-party mice that received PD-treated splenocytes at the time of transplant lived 100 days without evidence of GVHD. In contrast, all mice that received untreated primed splenocytes and third-party mice that received PD-treated splenocytes died of lethal GVHD. To evaluate the preservation of antiviral immune responses, acute lymphocytic choriomeningitis virus (LCMV) infection was employed. After PD, expansion of antigen-specific naïve CD8+ T cells and viral clearance remained fully intact. The high selectivity of this novel photosensitizer may have broad applications and provide alternative treatment options for patients with T lymphocyte mediated diseases.

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“…19 The introduction of a single fused julolidine or half-julolidine group gives a small increase in absorption maxima (λ max ), but larger shifts in λ max are realized by replacing the oxygen atom of the xanthylium core with the heavier chalcogen atoms S, Se, and Te. As the chalcogen atoms increase in size, the resulting rhodamines have decreasing quantum yields of fluorescence (Φ FL ) and increasing quantum yields for the generation of triplets and singlet oxygen [Φ( 1 O 2 )].…”

Section: Introductionmentioning

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

Cited by 11 publications

References 44 publications

Selenorhodamine photosensitizers with the Texas-red core for photodynamic therapy of cancer cells

Selenorhodamine photosensitizers with the Texas-red core for photodynamic therapy of cancer cells

Targeting T Cell Bioenergetics by Modulating P-Glycoprotein Selectively Depletes Alloreactive T Cells To Prevent Graft-versus-Host Disease

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

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