Design, synthesis, and discovery of stilbene derivatives based on lithospermic acid B as potent protein tyrosine phosphatase 1B inhibitors.
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.
Jung
Mankil
M
Department of Chemistry, Yonsei University, Seoul 120-749, Republic of Korea. mjung@yonsei.ac.kr
Lee
Yongnam
Y
Park
Moonsoo
M
Kim
Hanjo
H
Kim
Heekyeong
H
Lim
Eunyoung
E
Tak
Jungae
J
Sim
Minjoo
M
Lee
Dongeun
D
Park
Namsoo
N
Oh
Won Keun
WK
Hur
Kyu Yeon
KY
Kang
Eun Seok
ES
Lee
Hyun-Chul
HC
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
D000975:Antioxidants; D001572:Benzofurans; D053630:Depsides; D013267:Stilbenes; C076944:salvianolic acid B; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1