Polyamine conjugation of curcumin analogues toward the discovery of mitochondria-directed neuroprotective agents.
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.
Simoni
Elena
E
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Bergamini
Christian
C
Fato
Romana
R
Tarozzi
Andrea
A
Bains
Sandip
S
Motterlini
Roberto
R
Cavalli
Andrea
A
Bolognesi
Maria Laura
ML
Minarini
Anna
A
Hrelia
Patrizia
P
Lenaz
Giorgio
G
Rosini
Michela
M
Melchiorre
Carlo
C
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
D000970:Antineoplastic Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D011073:Polyamines; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; D003474:Curcumin