Bromophenols as inhibitors of protein tyrosine phosphatase 1B with antidiabetic properties.
ABSTRACT A series of bromophenol derivatives were synthesized and evaluated as protein tyrosine phosphatase 1B (PTP1B) inhibitors in vitro and in vivo based on bromophenol 4e (IC(50)=2.42 μmol/L), which was isolated from red algae Rhodomela confervoides. The results showed that all of the synthesized compounds displayed weak to good PTP1B inhibition at tested concentration. Among them, highly brominated compound 4g exhibited promising inhibitory activity against PTP1B with IC(50) 0.68 μmol/L, which was approximately fourfold more potent than lead compound 4e. Further, compound 4g demonstrated high selectivity against other PTPs (TCPTP, LAR, SHP-1 and SHP-2). More importantly, in vivo antidiabetic activities investigations of compound 4g also demonstrated inspiring results.
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ABSTRACT: Five bromophenols isolated from three Rhodomelaceae algae (Laurencia nipponica, Polysiphonia morrowii, Odonthalia corymbifera) showed inhibitory effects against glucose 6-phosphate dehydrogenase (G6PD). Among them, the symmetric bromophenol dimer (5) showed the highest inhibitory activity against G6PD.Marine Drugs 01/2013; 11(10):4050-7. · 3.98 Impact Factor
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ABSTRACT: Introduction: Thromboembolic incidences have increased nearly 33% in the past decade and directly affect nearly 0.5% of the population. Heparin, warfarin and current direct thrombin inhibitors (DTIs), the primary anticoagulants of choice, suffer from several drawbacks. Thus, the search for an antithrombotic devoid of adverse effect continues in earnest. Areas covered: Literature search covering PubMed, SciFinder(™) Scholar, Web of Knowledge, Espacenet, PatentScope and Google Patent Search was used to uncover > 35 patents describing new chemical entities and advances in DTI technologies. Our search uncovered considerable emphasis on the development of larger more complex molecules such as peptide-based inhibitors, prodrug derivatives, bivalent tryptophan zippers, triple action inhibitors and allosteric inhibitors. Advances in formulation technologies for clinically relevant DTIs have also been made. Expert opinion: Thrombin is a multifaceted, dynamic enzyme with both coagulant and anticoagulant functions. Newer DTIs are attempting to fine tune thrombin's activity by targeting allosteric sites or by site-specific targeting of clotting. The complexity of thrombin's functions is driving the design of complex anticoagulants. Advancements in formulations and production processes have attempted to make traditional DTIs more cost effective to produce. The literature reveals a trend to develop a thrombin 'modulator' rather than an 'inhibitor.'Expert Opinion on Therapeutic Patents 10/2013; · 3.53 Impact Factor
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ABSTRACT: Marine algae contain various bromophenols with a variety of biological activities, including antimicrobial, anticancer, and anti-diabetic effects. Here, we briefly review the recent progress in researches on the biomaterials from marine algae, emphasizing the relationship between the structure and the potential anti-diabetic applications. Bromophenols from marine algae display their hyperglycemic effects by inhibiting the activities of protein tyrosine phosphatase 1B, α-glucosidase, as well as other mechanisms.Journal of Ocean University of China 11(4).