title: Synthesis and tubulin-binding properties of non-symmetrical click C5-curcuminoids.
abstract: A click-type entry into shortened curcuminoids of the diarylpentanoid type has been developed. The reaction is ideally suited to generate non-symmetrical analogues of curcumin, a class of natural products difficult to access but of growing biomedical relevance and special mechanistic interest to investigate the unique binding mode of curcumin to tubulin. Investigation of a series of click diarylpentane curcuminoids and their pyrazole adducts in various cellular tubulin functional assays validated this class of compounds as a novel type of anti-mitotic agents, evidencing structure-activity relationships, and identifying the pyrazole adduct 4k as a promising lead.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Via Bovio 6, Novara 28100, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Caldarelli
authors.forename: Eleonora
authors.initials: E
authors.lastname: Penucchini
authors.forename: Diego
authors.initials: D
authors.lastname: Caprioglio
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.forename: Alberto
authors.initials: A
authors.lastname: Minassi
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D006801:Humans; D011720:Pyrazoles / Q000737:chemistry; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
chemical_list: D011720:Pyrazoles; D014404:Tubulin; D050257:Tubulin Modulators; C031280:pyrazole; D003474:Curcumin
keywords: Antimitotic agents; Click chemistry; Curcumin; Curcuminoids; Tubulin