title: Design, synthesis, and discovery of stilbene derivatives based on lithospermic acid B as potent protein tyrosine phosphatase 1B inhibitors.
abstract: Dihydroxy stilbene derivatives were designed based on lithospermic acid B and were prepared from 4-(chloromethyl)benzoic acid. The inhibitory activities of the novel compounds against protein tyrosine phosphatase 1B (PTP1B) were evaluated. 3,4-Dihydroxy stilbene carbonyl compounds (7, 11b, 27b) inhibited PTP1B with IC50 values comparable to molybdate, while the conjugation-extended compound (15b) showed inhibition 3-fold better than preclinical RK682. The introduction of electron withdrawing groups or amides into the second phenyl ring, or extension of the conjugation into the stilbene molecule may increase stability of the generated radicals.
authors.affiliation: Department of Chemistry, Yonsei University, Seoul 120-749, Republic of Korea. mjung@yonsei.ac.kr
authors.forename: Mankil
authors.initials: M
authors.lastname: Jung
authors.forename: Yongnam
authors.initials: Y
authors.lastname: Lee
authors.forename: Moonsoo
authors.initials: M
authors.lastname: Park
authors.forename: Hanjo
authors.initials: H
authors.lastname: Kim
authors.forename: Heekyeong
authors.initials: H
authors.lastname: Kim
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Lim
authors.forename: Jungae
authors.initials: J
authors.lastname: Tak
authors.forename: Minjoo
authors.initials: M
authors.lastname: Sim
authors.forename: Dongeun
authors.initials: D
authors.lastname: Lee
authors.forename: Namsoo
authors.initials: N
authors.lastname: Park
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Oh
authors.forename: Kyu Yeon
authors.initials: KY
authors.lastname: Hur
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
authors.forename: Hyun-Chul
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001572:Benzofurans / Q000737:chemistry* / Q000494:pharmacology; D053630:Depsides / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D001572:Benzofurans; D053630:Depsides; D013267:Stilbenes; C076944:salvianolic acid B; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1