title: Polyamine conjugation of curcumin analogues toward the discovery of mitochondria-directed neuroprotective agents.
abstract: Mitochondria-directed antioxidants 2-5 were designed by conjugating curcumin congeners with different polyamine motifs as vehicle tools. The conjugates emerged as efficient antioxidants in mitochondria and fibroblasts and also exerted a protecting role through heme oxygenase-1 activation. Notably, the insertion of a polyamine function into the curcumin-like moiety allowed an efficient intracellular uptake and mitochondria targeting. It also resulted in a significant decrease in the cytotoxicity effects. 2-5 are therefore promising molecules for neuroprotectant lead discovery.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Simoni
authors.forename: Christian
authors.initials: C
authors.lastname: Bergamini
authors.forename: Romana
authors.initials: R
authors.lastname: Fato
authors.forename: Andrea
authors.initials: A
authors.lastname: Tarozzi
authors.forename: Sandip
authors.initials: S
authors.lastname: Bains
authors.forename: Roberto
authors.initials: R
authors.lastname: Motterlini
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Bolognesi
authors.forename: Anna
authors.initials: A
authors.lastname: Minarini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Hrelia
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lenaz
authors.forename: Michela
authors.initials: M
authors.lastname: Rosini
authors.forename: Carlo
authors.initials: C
authors.lastname: Melchiorre
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D011073:Polyamines / Q000138:chemical synthesis* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D011073:Polyamines; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; D003474:Curcumin