title: Antitumor agents. 250. Design and synthesis of new curcumin analogues as potential anti-prostate cancer agents.
abstract: In a continuing study of curcumin analogues as potential drug candidates to treat prostate cancer at both androgen-dependent and androgen-refractory stages, we designed and synthesized over 40 new analogues classified into four series: monophenyl analogues (series A), heterocycle-containing analogues (series B), analogues bearing various substituents on the phenyl rings (series C), and analogues with various linkers (series D). These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells, seven only against LNCaP, and one solely against PC-3. This study established an advanced structure-activity relationship (SAR), and these correlations will guide the further design of new curcumin analogues with better anti-prostate cancer activity.
authors.affiliation: Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7360, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Nyarko
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Chin-Chung
authors.initials: CC
authors.lastname: Wu
authors.forename: Ching-Yuan
authors.initials: CY
authors.lastname: Su
authors.forename: Charles C-Y
authors.initials: CC
authors.lastname: Shih
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000726:Androgen Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D009376:Neoplasms, Hormone-Dependent; D011471:Prostatic Neoplasms; D011944:Receptors, Androgen / Q000235:genetics; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D008156:Luciferases; D003474:Curcumin