title: Selenorhodamine photosensitizers for photodynamic therapy of P-glycoprotein-expressing cancer cells.
abstract: 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.
authors.affiliation: Department of Chemistry, University at Buffalo, The State University of New York , Buffalo, New York 14260-3000, United States.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Hill
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Linder
authors.forename: Kellie S
authors.initials: KS
authors.lastname: Davies
authors.forename: Geri A
authors.initials: GA
authors.lastname: Sawada
authors.forename: Janet
authors.initials: J
authors.lastname: Morgan
authors.forename: Tymish Y
authors.initials: TY
authors.lastname: Ohulchanskyy
authors.forename: Michael R
authors.initials: MR
authors.lastname: Detty
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D061985:Madin Darby Canine Kidney Cells / Q000187:drug effects; D051379:Mice; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012235:Rhodamines / Q000493:pharmacokinetics; D026082:Singlet Oxygen / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D018675:Toxicity Tests; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016566:Organoselenium Compounds; D017319:Photosensitizing Agents; D012235:Rhodamines; D026082:Singlet Oxygen; D004317:Doxorubicin; D014700:Verapamil