title: Synthesis of gossypol atropisomers and derivatives and evaluation of their anti-proliferative and anti-oxidant activity.
abstract: Gossypol 1, gossypolone 2, and a series of bis 3 and half Schiff's bases 4 of gossypol were synthesised and tested for anti-proliferative and anti-oxidant activity. (-)-Gossypol (-)-1 was the most potent inhibitor of the proliferation of the HPV-16 keratinocyte cell line (using an MTT viability assay) with a GI50 of 4.8 microM. The bis Schiff's base of (-)-gossypol with L-tyrosine ethyl ester (-)-3b was the most potent inhibitor of iron/ascorbate dependent lipid peroxidation (using the thiobarbituric acid test), with an IC50 of 11.7 microM, with (-)-gossypol being the next most potent of the series, with an IC50 of 13.1 microM. The results from these initial assays suggest that gossypol, as either a racemic mixture rac-1, or the individual atropisomers (-)-1 or (+)-1, has potential for the treatment of psoriasis.
authors.affiliation: Sunderland Pharmacy School, University of Sunderland, Wharncliffe Street, Sunderland SR1 3SD, UK.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Dodou
authors.forename: Rosaleen J
authors.initials: RJ
authors.lastname: Anderson
authors.forename: W John
authors.initials: WJ
authors.lastname: Lough
authors.forename: David A P
authors.initials: DA
authors.lastname: Small
authors.forename: Michael D
authors.initials: MD
authors.lastname: Shelley
authors.forename: Paul W
authors.initials: PW
authors.lastname: Groundwater
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003272:Contraceptive Agents, Male / Q000138:chemical synthesis / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006072:Gossypol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012545:Schiff Bases; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D003272:Contraceptive Agents, Male; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D012545:Schiff Bases; D007501:Iron; D006072:Gossypol; D001205:Ascorbic Acid