title: Three-Arm, Biotin-Tagged Carbazole-Dicyanovinyl-Chlorambucil Conjugate: Simultaneous Tumor Targeting, Sensing, and Photoresponsive Anticancer Drug Delivery.
abstract: The design, synthesis, and in vitro biological studies of a biotin-carbazole-dicyanovinyl-chlorambucil conjugate (Bio-CBZ-DCV-CBL; 6) are reported. This conjugate (6) is a multifunctional single-molecule appliance composed of a thiol-sensor DCV functionality, a CBZ-derived phototrigger as well as fluorescent reporter, and CBL as the anticancer drug, and Bio as the cancer-targeting ligand. In conjugate 6, the DCV bond undergoes a thiol-ene click reaction at pH<7 with intracellular thiols, thereby shutting down internal charge transfer between the donor CBZ and acceptor DCV units, resulting in a change of the fluorescence color from green to blue, and thereby, sensing the tumor microenvironment. Subsequent photoirradiation results in release of the anticancer drug CBL in a controlled manner.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kharagpur, 721302, West Bengal, India.
authors.forename: Yarra
authors.initials: Y
authors.lastname: Venkatesh
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kharagpur, 721302, West Bengal, India.
authors.forename: S
authors.initials: S
authors.lastname: Karthik
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology Kharagpur, 721302, West Bengal, India.
authors.forename: Y
authors.initials: Y
authors.lastname: Rajesh
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology Kharagpur, 721302, West Bengal, India.
authors.forename: Mahitosh
authors.initials: M
authors.lastname: Mandal
authors.affiliation: Biomaterials Group, Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
authors.forename: Avijit
authors.initials: A
authors.lastname: Jana
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kharagpur, 721302, West Bengal, India.
authors.forename: N D Pradeep
authors.initials: ND
authors.lastname: Singh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D001710:Biotin / Q000737:chemistry*; D002227:Carbazoles / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002699:Chlorambucil / Q000737:chemistry* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008027:Light; D051379:Mice; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D010782:Photolysis / Q000528:radiation effects; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D004337:Drug Carriers; D002699:Chlorambucil; D001710:Biotin
keywords: antitumor agents; cancer; drug delivery; glutathione sensing; photochemistry