title: Triazole-curcuminoids: A new class of derivatives for 'tuning' curcumin bioactivities?
abstract: Curcumin is a unique blend of pharmacophores responsible for the pleiotropy of this natural pigment. In the present study we have replaced the 1,3-dicarbonyl moiety with a 1,2,3-triazole ring to furnish a new class of triazole-curcuminoids as a possible strategy to generate new compounds with different potency and selectivity compared to curcumin. We obtained a proof-of-principle library of 28 compounds tested for their cytotoxicity (SY-SY5Y and HeLa cells) and for their ability to inhibit NF-κB. Furthermore, we also generated 1,3-dicarbonyl curcuminoids of selected click compounds. Triazole-curcuminoids lost their ability to be Michael's acceptors, yet maintained some of the features of the parent compounds and disclosed new ones. In particular, we found that some compounds were able to inhibit NF-κB without showing cytotoxicity, while others, unlike curcumin, activated NF-κB signalling. This validates the hypothesis that click libraries can be used to investigate the biological activities of curcumin as well as generate analogs with selected features.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Via Bovio 6, Novara 28100, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Caprioglio
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Via Bovio 6, Novara 28100, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Torretta
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Via Bovio 6, Novara 28100, Italy.
authors.forename: Maila
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Via Bovio 6, Novara 28100, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Travelli
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Via Bovio 6, Novara 28100, Italy.
authors.forename: Ambra A
authors.initials: AA
authors.lastname: Grolla
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Via Bovio 6, Novara 28100, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Condorelli
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Via Bovio 6, Novara 28100, Italy. Electronic address: armando.genazzani@uniupo.it.
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Via Bovio 6, Novara 28100, Italy. Electronic address: alberto.minassi@uniupo.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Minassi
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D016328:NF-kappa B; D014230:Triazoles; D003474:Curcumin
keywords: 1,3-Dipolar cycloaddition; Click chemistry; Curcumin; Curcuminoids; NF-κB