HPN, a synthetic analogue of bromophenol from red alga Rhodomela confervoides: synthesis and anti-diabetic effects in C57BL/KsJ-db/db mice

Mar Drugs. 2013 Jan 30;11(2):350-62. doi: 10.3390/md11020350.

Abstract

3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-(isopropoxymethyl)benzyl)benzene-1,2-diol (HPN) is a synthetic analogue of 3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(ethoxymethyl)benzyl)benzene-1,2-diol (BPN), which is isolated from marine red alga Rhodomela confervoides with potent protein tyrosine phosphatase 1B (PTP1B) inhibition (IC(50) = 0.84 μmol/L). The in vitro assay showed that HPN exhibited enhanced inhibitory activity against PTP1B with IC(50) 0.63 μmol/L and high selectivity against other PTPs (T cell protein tyrosine phosphatase (TCPTP), leucocyte antigen-related tyrosine phosphatase (LAR), Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1) and SHP-2). The results of antihyperglycemic activity using db/db mouse model demonstrated that HPN significantly decreased plasma glucose (P < 0.01) after eight weeks treatment period. HPN lowered serum triglycerides and total cholesterol concentration in a dose-dependent manner. Besides, both of the high and medium dose groups of HPN remarkably decreased HbA1c levels (P < 0.05). HPN in the high dose group markedly lowered the insulin level compared to the model group (P < 0.05), whereas the effects were less potent than the positive drug rosiglitazone. Western blotting results showed that HPN decreased PTP1B levels in pancreatic tissue. Last but not least, the results of an intraperitoneal glucose tolerance test in Sprague-Dawley rats indicate that HPN have a similar antihyperglycemic activity as rosiglitazone. HPN therefore have potential for development as treatments for Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzyl Compounds / chemistry
  • Benzyl Compounds / pharmacology*
  • Blood Glucose / drug effects
  • Body Weight
  • Catechols / chemistry
  • Catechols / pharmacology*
  • Diabetes Mellitus / drug therapy*
  • Dose-Response Relationship, Drug
  • Drinking / drug effects
  • Eating / drug effects
  • Glucose Tolerance Test
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Mice
  • Mice, Inbred NOD
  • Molecular Structure
  • Rats
  • Rats, Sprague-Dawley
  • Rhodophyta / chemistry*

Substances

  • 3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(isopropoxymethyl)benzyl)benzene-1,2-diol
  • Benzyl Compounds
  • Blood Glucose
  • Catechols
  • Hypoglycemic Agents