Jin Hyo Kim

Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities

Five flavonols (3, 5, and 9-11) were isolated from Rhodiola rosea, and compared with commercially available flavonoids (1, 2, 4, 6-8, and 12-14) to facilitate analysis of their structure-activity relationship (SAR). All compounds (1-14) showed neuraminidase inhibitory activities with IC(50) values ranging from 0.8 to 56.9 microM. The in vitro anti-influenza virus activities of flavonoids 1-6, 8-12, and 14 were evaluated using two influenza viral strains, H1N1 (A/PR/8/34) and H9N2 (A/Chicken/Korea/MS96/96), testing their ability to reduce virus-induced cytopathic effect (CPE) in MDCK cells. We found that the activity of these compounds ranged from 30.2 to 99.1 microM against H1N1- and 18.5 to 133.6 microM against H9N2-induced CPE. Of compounds 1-14, gossypetin (6) exhibited the most potent inhibitory activity, with IC(50) values of 0.8 and 2.6 microM on neuraminidases from Clostridium perfringens and recombinant influenza virus A (rvH1N1), respectively. In contrast, kaempferol (3) exhibited the highest activity against two influenza viruses, H1N1 and H9N2 with EC(50) values of 30.2 and 18.5 microM, respectively. Activity depended on the position and number of hydroxy groups on the flavonoids backbone. In kinetic studies, all isolated compounds behaved as noncompetitive inhibitors.

Pterocarpans and flavanones from Sophora flavescens displaying potent neuraminidase inhibition

Pterocarpans (1-3) and flavanones (4-10) were isolated from Sophora flavescens and screened for their ability to inhibit neuraminidase (an enzyme crucial in the proliferation of the influenza virus). The majority of inhibitors were shown to have IC(50) values of 20 microM or below. Interestingly, pterocarpan 1 emerged as the best inhibitor with an IC(50) of 1.4 microM. We were thus able to prove that the pterocarpan skeleton is a new class of lead structure for neuraminidase inhibitors. Our studies reveal that the IC(50) has a marked dependence upon structure in the case of the pterocarpans but much less so for the flavanones. Kinetic analysis disclosed that all inhibitors are noncompetitive. Our molecular docking experiment resulted that the most potent pterocarpan-derived inhibitor 1 may bind to another binding pocket adjacent to the active site.

Characteristic of neuraminidase inhibitory xanthones from Cudrania tricuspidata

Natural polyphenolic compounds generally transpire to show relatively low inhibition against glycosidase including neuraminidase. In addition the inhibition modes of such compounds are rarely competitive. In this manuscript, a series of xanthone derivatives from Cudrania tricuspidata are shown to display nanomolar inhibitor activity against neuraminidase (EC 3.2.1.18) as well as competitive inhibition modes. Compound 8 bearing vicinal dihydroxy group on the A-ring displays nanomolar activity (IC(50)=0.08+/-0.01 microM), a 200-fold increase in activity relative to that of the first reported xanthone-derived neuraminidase inhibitor, mangiferin (IC(50)=16.2+/-4.2 microM). The 6,7-vicinal dihydroxy group plays a crucial role for inhibitory activity because compound 4, which has one of these hydroxyl groups prenylated was inactive (33% at 200 microM), whereas other compounds (1-3 and 6-8) showed nanomolar activity (0.08-0.27 microM) and competitive inhibition modes. Interestingly all inhibitors manifested enzyme isomerization inhibition against neuraminidase. The most potent inhibitor, compound 8 showed similar interaction with a transition-state analogue of neuraminic acid in active site.

Inhibitory Evaluation of Sulfonamide Chalcones on β-Secretase and Acylcholinesterase

The action of β-secretase (BACE1) is strongly correlated with the onset of Alzheimer’s disease (AD). Aminochalcone derivatives were examined for their ability to inhibit BACE1. Parent aminochalcones showed two digit micromolar IC50s against BACE1. Potency was enhanced 10-fold or more by introducing benzenesulfonyl derivatives to the amino group: 1 (IC50 = 48.2 μM) versus 4a (IC50 = 1.44 μM) and 2 (IC50 = 17.7 μM) versus 5a (IC50 = 0.21 μM). The activity was significantly influenced by position and number of hydroxyl groups on the chalcone B-ring: 3,4-dihydroxy 5a (IC50 = 0.21 μM) > 4-hydroxy 4a (IC50 = 1.44 μM) > 2,4-dihydroxy 6 (IC50 = 3.60 μM) > 2,5-dihydroxy 7 (IC50 = 16.87 μM) > des hydroxy 4b (IC50 = 168.7 μM). Lineweaver-Burk and Dixon plots and their secondary replots indicate that compound 5a was a mixed inhibitor with reversible and time-dependent behavior. Potent BACE1 inhibitors 4a,c,f, 5a–c showed moderate inhibition against two other enzymes implicated in AD pathogenesis, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC50s ranging between 56.1 ~ 95.8 μM and 19.5 ~ 79.0 μM, respectively.

Diastereoselective synthesis of syn-aminoalcohols via contributing CH-π interaction: simple synthesis of (-)-bestatin

Abstract 1 H NMR and X-ray crystallography studies revealed that a CH-π and chelation control in aromatic aminoaldehydes ( 1 – 6 ) effects a highly diastereoselective addition to afford optically active syn -aminoalcohols ( 1a – 6a ). This methodology was applied to the synthesis of (−)-bestatin.

Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive Oxygen Species-Mediated Apoptosis in Lung Cancer Cells and Decreases Xenograft Tumor Growth

Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI‐H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl‐2 and Bcl‐xL, and upregulation of Bax, suggesting that caspase‐mediated pathways were involved in MSF‐induced apoptosis. ROS activation of the mitogen‐activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI‐H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production. Copyright

Residual perfluorochemicals in the biochar from sewage sludge

Biochar has been recently considered as a candidate for soil amendment and soil remediation. Some pollutants have been screened in the biochar for safety purposes except for perfluorochemicals (PFCs). In this study, the contamination of biochars from plant residues and sewage sludge with perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) was examined. The total residual concentrations of PFOA and PFOS in the sludge biochar were 15.8-16.9 ng/g and these values did not decrease significantly after pyrolysis. On the other hand, these PFCs were not found in the biochar from plant sources. In conclusion, the use of the sludge biochar in the agricultural environment should be re-evaluated, since the concentrations of PFCs in the sewage sludge showed no significant decrease after thermal process.

Investigation on Biogenic Amines in Plant-based Minor Korean Fermented Foods

Ten major residual biogenic amines including toxic histamine and tyramine were investigated in the plant-based minor Korean fermented food. From the analyses of pickled vegetables, fermented vegetable extracts, fermented tea, black garlic and herbal rice wines, more than 100 mg/kg of histamine were found in pickled soy leaf and pickled mulberry leaf, and also over 1,000 mg/kg of total biogenic amines were found in pickled soy leaf. No sample was found over in black garlic, fermented tea, fermented vegetable extracts and herbal rice wine, less than 100 mg/kg of histamine and/or 1,000 mg/kg of total biogenic amines were observed. Interestingly, all the tested rice wines were found to be over 100 mg/kg of agmatine residue.

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) concentrations in the South Korean agricultural environment: A national survey

Abstract Research on the occurrence of perfluorochemicals (PFCs) such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in the agricultural environment is lacking, in spite of their potential risk via food chain transfer from aquatic and soil-plant systems to animals and/or humans. In the present study, for the first time, soil and water samples collected from 243 different agricultural sites adjacent to waste water treatment plants (WWTPs) belonging to 81 cities and 5 provinces with different levels of industrialization in South Korea were monitored for concentrations of PFOS and PFOA by use of solid phase extraction and liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Significant mean concentrations of PFOA (0.001–0.007 µg L −1 water and −1 soil) and PFOS (0.001–0.22 µg L −1 water and −1 soil) were found in all samples. Concentrations of PFCs in soils were high, highlighting that soil is an important sink for PFCs in the agricultural environment. Samples from near WWTPs in Gyeongsang Province contained the highest concentrations of PFOS and PFOA, reflecting the concentration of heavy industry in the province. The concentrations of PFCs in agricultural water (most samples −1 ) and soils (most samples −1 ) from South Korea were less than acceptable guideline values, indicating that South Korea is not a hotspot of PFOS and PFOA contamination and that there is negligible risk to human and ecological health from these chemicals. However, further studies investigating the seasonal variation in PFOA, PFOS and other perfluorochemical concentrations in the agricultural environment are needed.

Diastereoselective iodoamidation of 3-acetyloxybut-1-enylamines: simple synthesis of a precursor of aza sugars involving a pyrrolidine ring

3-Acetyloxybut-1-enylamines 3–9 were easily transformed using iodine to pyrrolidine derivatives 3a–9a, precursors for aza sugars, via a diastereoselective iodoamidation.