Design, synthesis, and biological evaluation of bromophenol derivatives as protein tyrosine phosphatase 1B inhibitors.
3-Bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (BDB) is a bromophenol purified from the marine red alga Rhodomela confervoides and exhibits potent protein tyrosine phosphatase 1B (PTP1B) inhibition (IC(50)  = 1.7 µmol/L). In an effort to improve the PTP1B inhibitory activity, a series of derivatives were designed, synthesized, and evaluated in vitro. The preliminary structure-activity relationship indicated that the tricyclic scaffold and multi-bromine atoms (four to five) attached to the aryl rings are important for PTP1B inhibition. Among these, compound 26 exhibited remarkable inhibitory activity against PTP1B with an IC(50)  of 0.89 µmol/L, which was approximately two-fold more potent than the initial lead compound BDB.
Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.
Bo
B
Jiang
Dayong
D
Shi
Yongchao
Y
Cui
Shuju
S
Guo
D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002396:Catechols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C576799:3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol; D001559:Benzhydryl Compounds; D002396:Catechols; D004791:Enzyme Inhibitors; D010636:Phenols; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1