Fluorophore-tagged pharmacophores for antitumor cytotoxicity: Modified chiral lipidic dialkynylcarbinols for cell imaging.
Chiral lipidic dialkynylcarbinols (DACs), recently highlighted as antitumoral pharmacophores, have been conjugated to difluoroboron-dipyrromethene (bodipy), 7-hydroxy-coumarine, and 7-nitro-benzoxadiazole (NBD) fluorophore motifs through triazole clips. The labeled lipids preserve cytotoxic activity against HCT116 cells, and fluorescence microscopy of the stained cells showed clear signals in the intra-cellular membrane system. While the bodipy conjugate also labels lipid droplets very brightly, as expected, the coumarine and NBD probes appear as promising specific tools for the identification of the intra-cellular targets of DACs' cytotoxicity.
UPR CNRS 8241, LCC (Laboratoire de Chimie de Coordination), 205 Route de Narbonne, BP 44099, 31077 Toulouse cedex 4, France; Institut de Chimie de Toulouse, ICT-FR2599, Université de Toulouse-Université Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse, France; UMR CNRS 5068, LSPCMIB, Université de Toulouse, Université Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse cedex 9, France; Department of Chemistry, Taras Shevchenko National University of Kyiv, Volodymyrska Street 64/13, Kyiv 01601, Ukraine.
Dymytrii
D
Listunov
UMR CNRS 5089, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 Route de Narbonne, 31077 Toulouse cedex, France.
Serge
S
Mazères
Department of Chemistry, Taras Shevchenko National University of Kyiv, Volodymyrska Street 64/13, Kyiv 01601, Ukraine.
Yulian
Y
Volovenko
UMR CNRS 5089, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 Route de Narbonne, 31077 Toulouse cedex, France. Electronic address: joly@ipbs.fr.
Etienne
E
Joly
UMR CNRS 5068, LSPCMIB, Université de Toulouse, Université Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse cedex 9, France. Electronic address: genisson@chimie.ups-tlse.fr.
Yves
Y
Génisson
UPR CNRS 8241, LCC (Laboratoire de Chimie de Coordination), 205 Route de Narbonne, BP 44099, 31077 Toulouse cedex 4, France; Institut de Chimie de Toulouse, ICT-FR2599, Université de Toulouse-Université Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse, France. Electronic address: valerie.maraval@lcc-toulouse.fr.
Valérie
V
Maraval
UPR CNRS 8241, LCC (Laboratoire de Chimie de Coordination), 205 Route de Narbonne, BP 44099, 31077 Toulouse cedex 4, France; Institut de Chimie de Toulouse, ICT-FR2599, Université de Toulouse-Université Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse, France. Electronic address: chauvin@lcc-toulouse.fr.
Remi
R
Chauvin
D000970:Antineoplastic Agents / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001896:Boron Compounds / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005456:Fluorescent Dyes / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry*; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D000432:Methanol / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging; D015394:Molecular Structure; D013329:Structure-Activity Relationship
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000970:Antineoplastic Agents; D001896:Boron Compounds; D005456:Fluorescent Dyes; D008055:Lipids; D000432:Methanol
1,2,3-Triazole; Alkynylcarbinol; Antitumoral cytotoxicity; Asymmetric synthesis; Cell imaging; Click chemistry; Fluorophore; Lipid