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dc.contributor.authorPerrone, Maria Grazia
dc.contributor.authorVitale, Paola
dc.contributor.authorMiciaccia, Morena
dc.contributor.authorFerorelli, Savina
dc.contributor.authorCentonze, Antonella
dc.contributor.authorSolidoro, Roberta
dc.contributor.authorMunzone, Cristina
dc.contributor.authorBonaccorso, Carmela
dc.contributor.authorFortuna, Cosimo Gianluca
dc.contributor.authorKleinmanns, Katrin
dc.contributor.authorBjørge, Line
dc.contributor.authorScilimati, Antonio
dc.date.accessioned2022-12-08T12:20:56Z
dc.date.available2022-12-08T12:20:56Z
dc.date.created2022-09-12T12:34:17Z
dc.date.issued2022
dc.identifier.issn1424-8247
dc.identifier.urihttps://hdl.handle.net/11250/3036775
dc.description.abstractThe identification and removal of all gross and microscopic tumor to render the patient disease free represents a huge challenge in ovarian cancer treatment. The presence of residual disease is an independent negative prognostic factor. Herein, we describe the synthesis and the “in vitro” evaluation of compounds as cyclooxygenase (COX)-1 inhibitors, the COX-1 isoform being an ovarian cancer biomarker, each bearing fluorochromes with different fluorescence features. Two of these compounds N-[4-(9-dimethylimino-9H-benzo[a]phenoxazin-5-ylamino) butyl]-2-(3,4-bis(4-methoxyphenyl)isoxazol-5-yl)acetamide chloride (RR11) and 3-(6-(4-(2-(3,4-bis(4-methoxyphenyl)isoxazole-5-yl)acetamido)butyl)amino-6-oxohexyl)-2-[7-(1,3-dihydro-1,1-dimethyl-3-ethyl 2H-benz[e]indolin-2-yl-idene)-1,3,5-heptatrienyl]-1,1-dimethyl-3-(6-carboxilato-hexyl)-1H-benz[e]indolium chloride, 23 (MSA14) were found to be potent and selective inhibitors of cyclooxygenase (COX)-1 “in vitro”, and thus were further investigated “in vivo”. The IC50 values were 0.032 and 0.087 µM for RR11 and 23 (MSA 14), respectively, whereas the COX-2 IC50 for RR11 is 2.4 µM while 23 (MSA14) did not inhibit COX-2 even at a 50 µM concentration. Together, this represented selectivity index = 75 and 874, respectively. Structure-based virtual screening (SBVS) performed with the Fingerprints for Ligands and Proteins (FLAP) software allowed both to differentiate highly active compounds from less active and inactive structures and to define their interactions inside the substrate-binding cavity of hCOX1. Fluorescent probes RR11 and 23 (MSA14), were used for preliminary near-infrared (NIR) fluorescent imaging (FLI) in human ovarian cancer (OVCAR-3 and SKOV-3) xenograft models. Surprisingly, a tumor-specific signal was observed for both tested fluorescent probes, even though this signal is not linked to the presence of COX-1.en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleFluorochrome Selection for Imaging Intraoperative Ovarian Cancer Probesen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2022 the authorsen_US
dc.source.articlenumber668en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.3390/ph15060668
dc.identifier.cristin2050764
dc.source.journalPharmaceuticalsen_US
dc.identifier.citationPharmaceuticals. 2022, 15 (6), 668.en_US
dc.source.volume15en_US
dc.source.issue6en_US


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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal