Synthesis and protein tyrosine phosphatase 1B inhibition activities of two new synthetic bromophenols and their methoxy derivatives

3-bromo-4,5-bis（2,3-dibromo-4,5-dihydroxybenzyl）-l,2-benzenediol （1） is a natural bromophenol isolated from the red algae Rhodomela confervoides that exhibits significant inhibition against protein tyrosine phosphatase 1B （PTP1B）. Based on its activity, we synthesized two new synthetic bromophenols and their methoxy derivatives from vanillin using the structure of natural bromophenol 1 as a scaffold. The structures of these bromophenols were elucidated from H NMR, 13C NMR, and high resolution electron ionization mass spectrometry as 2,3-dibromo-1-（2＇-bromo-6＇-（3＂,4＂-dimethoxybenzyl）- 3 ＇,4 ＇-dimethoxybenzyl）-4,5 -dimethoxybenzene （2）, 2,3-dibromo- 1 -（2 ＇-bromo-6＇-（2 ＂-bromo-4＂,5 ＂-dimethoxy- benzyl）-3＇,4＇-dimethoxybenzyl）-4,5-dimethoxybenzene （3）, 3,4-dibromo-5-（2＇-bromo-6＇-（2＂-bromo-4＂,5＂- dihydroxybenzyl）-3＇,4＇-dihydroxybenzyl）pyrocatechol （4） and 3,4-dibromo-5-（2＇-bromo-6＇-（3＂,4＂- dihydroxybenzyl）-3＇,4＇-dihydroxybenzyl）pyrocatechol （5）. PTP1B inhibition activities of these compounds were evaluated using a colorimetric assay, and compounds 3 and 4 demonstrated interesting activity against PTP1B.

Isolation of Microcystins from the Cyanobacterium Planktothrix rubescens Strain No80

Three minor microcystins have been isolated from a Planktothrix rubescens strain.Their structures have been elucidated by one-and two-dimensional NMR spectroscopy and high-resolution tandem mass spectrometry as the compounds[Asp^(3),(E)-Dhb^(7)]MC-LY(1),[Asp^(3),(E)-Dhb^(7)]MC-HtyW(2),and[Asp^(3),(E)-Dhb^(7)]MC-LW(3).The amino acids found at the variable positions 2 and 4 of the microcystin core structure are in accordance with the predicted amino acid substrate activation selectivities of the non-ribosomal peptide synthetases McyA and McyB described earlier for this strain.All structural microcystin variants produced by this strain were shown to inhibit protein phosphatase 1 in the nanomolar range.

Degradation and detoxification of microcystin-LR in drinking water by sequential use of UV and ozone

Microcystins （MCs） produced by cyanobacteria are strong hepatotoxins and classified as possible carcinogens. MCs pose a considerable threat to human health through tainted drinking and surface waters. Herein filtrated water from a waterworks in Harbin, China, was spiked with microcysfin-LR （MC-LR） extracted from a toxic scum of microcystis aeruginosa, and the spiked sample waters were treated using UV irradiation with consequent ozonation process （UV/O3）, compared with ozonation at a dose range commonly applied in water treatment plants, UV irradiation at 254 nm and UV irradiation combined with ozonation （UV＋O3）, respectively. The remaining of toxins were analyzed using high-performance liquid chromatography and also determined using a protein phosphatase type 2A inhibition assay, which was utilized to evaluate the reduction in toxicity. Results indicated that in comparison to other three processes （O3, UV, and UV＋O3）, UV/O3 process could effectively decrease both the concentration and toxicity of MC-LR at 100 μg/L level after 5 min UV irradiation with consequent 5 min ozonation at 0.2 mg/L （below 1 μg/L ）, while 0.5 mg/L ozone dose was required for the level below 0.1 μg/L. The addition of an UV treatment step to the existing treatment train may induce significant transformation of micropollutants and breaks down the natural organic matters into moieties unfavorable for ozone decomposition, stabilizing the ozone residual. These findings suggested that sequential use of UV and ozone may be a suitable method for the removal of these potentially hazardous microcystins from drinking water.