http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Oh, Joonseok,Liu, Haining,Park, Hyun Bong,Ferreira, Daneel,Jeong, Gil-Saeng,Hamann, Mark T.,Doerksen, Robert J.,Na, MinKyun Elsevier 2017 Biochimica et biophysica acta, General subjects Vol.1861 No.1
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Inhibition of fatty acid synthase (FAS) is regarded as a sensible therapeutic strategy for the development of optimal anti-cancer agents. Flavonoids exhibit potent anti-neoplastic properties.</P> <P><B>Methods</B></P> <P>The MeOH extract of <I>Sophora flavescens</I> was subjected to chromatographic analyses such as VLC and HPLC for the purification of active flavonoids. The DP4 chemical-shift analysis protocol was employed to investigate the elusive chirality of the lavandulyl moiety of the purified polyphenols. Induced Fit docking protocols and per-residue analyses were utilized to scrutinize structural prerequisites for hampering FAS activity. The FAS-inhibitory activity of the purified flavonoids was assessed via the incorporation of [<SUP>3</SUP>H] acetyl-CoA into palmitate.</P> <P><B>Results</B></P> <P>Six flavonoids, including lavandulyl flavanones, were purified and evaluated for FAS inhibition. The lavandulyl flavanone sophoraflavanone G (<B>2</B>) exhibited the highest potency (IC<SUB>50</SUB> of 6.7±0.2μM), which was more potent than the positive controls. Extensive molecular docking studies revealed the structural requirements for blocking FAS. Per-residue interaction analysis demonstrated that the lavandulyl functional group in the active flavonoids (<B>1</B>–<B>3</B> and <B>5</B>) significantly contributed to increasing their binding affinity towards the target enzyme.</P> <P><B>Conclusion</B></P> <P>This research suggests a basis for the <I>in silico</I> design of a lavandulyl flavonoid-based architecture showing anti-cancer effects via enhancement of the binding potential to FAS.</P> <P><B>General significance</B></P> <P>FAS inhibition by flavonoids and their derivatives may offer significant potential as an approach to lower the risk of various cancer diseases and related fatalities. <I>In silico</I> technologies with available FAS crystal structures may be of significant use in optimizing preliminary leads.</P> <P><B>Highlights</B></P> <P> <UL> <LI> FAS is a pertinent therapeutic target for the development of cancer agents. </LI> <LI> Lavandulyl flavanones exhibited powerful FAS inhibitory activity. </LI> <LI> The lavandulyl functional group contributed to enhancing their binding affinity. </LI> <LI> <I>In silico</I> design and optimization of flavonoid-based FAS inhibitors may be feasible. </LI> </UL> </P>
Quan, Khong Trong,Park, Hyun-Soo,Oh, Joonseok,Park, Hyun Bong,Ferreira, Daneel,Myung, Chang-Seon,Na, MinKyun American Chemical Society and American Society of 2016 Journal of natural products Vol.79 No.10
<P>The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are associated with cardiovascular diseases and related complications. Such deleterious proliferation and migration events are triggered by cytokines and growth factors, and among them, platelet-derived growth factor (PDGF) is recognized as the most potent inducer. Despite the genus Rubia being researched to identify valuable commercial and medicinal virtues, Rubia philippinensis has rarely been investigated. Nine arborinane-type triterpenoids (1-9) were identified from this underutilized plant species. In particular, 4 was identified as the first arborinane derivative carrying a ketocarbonyl motif at C-19. The presence of the cyclopentanone moiety and the associated configurational assignment were determined by utilizing NOE and coupling constant analysis. These compounds were assessed for their inhibitory potential on PDGF-induced proliferation and the migration of VSMCs. Treatment with 5 mu M compound 5 (62.6 +/- 10.7%) and compound 9 (41.1 +/- 4.7%) impeded PDGF-stimulated proliferation without exerting cytotoxicity. Compound 7 exhibited antimigration activity in a dose-dependent manner (38.5 +/- 3.0% at 10 mu M, 57.6 +/- 3.2% at 30 mu M). These results suggest that the arborinane-type triterpenoids may be a pertinent starting point for the development of cardiovascular drugs capable of preventing the intimal accumulation of VSMCs.</P>
Hwang, In Hyun,Oh, Joonseok,Zhou, Wei,Park, Seoyoung,Kim, Joo-Hyun,Chittiboyina, Amar G.,Ferreira, Daneel,Song, Gyu Yong,Oh, Sangtaek,Na, MinKyun,Hamann, Mark T. American Chemical Society and American Society of 2015 Journal of natural products Vol.78 No.3
<P/><P>Colorectal cancer has emerged as a major cause of death in Western countries. Down-regulation of β-catenin expression has been considered a promising approach for cytotoxic drug formulation. Eight 4,9-friedodrimane-type sesquiterpenoids (<B>1</B>–<B>8</B>) were acquired using the oxidative potential of <I>Verongula rigida</I> on bioactive metabolites from two <I>Smenospongia</I> sponges. Compounds <B>3</B> and <B>4</B> contain a 2,2-dimethylbenzo[<I>d</I>]oxazol-6(2<I>H</I>)-one moiety as their substituted heterocyclic residues, which is unprecedented in such types of meroterpenoids. Gauge-invariant atomic orbital NMR chemical shift calculations were employed to investigate stereochemical details with support of the application of advanced statistics such as CP3 and DP4. Compounds <B>2</B> and <B>8</B> and the mixture of <B>3</B> and <B>4</B> suppressed β-catenin response transcription (CRT) via degrading β-catenin and exhibited cytotoxic activity on colon cancer cells, implying that their anti-CRT potential is, at least in part, one of their underlying antineoplastic mechanisms.</P>
Oh, Joonseok,Quan, Khong Trong,Lee, Ji Sun,Park, InWha,Kim, Chung Sub,Ferreira, Daneel,Thuong, Phuong Thien,Kim, Young Ho,Na, MinKyun American Chemical Society and American Society of 2018 Journal of natural products Vol.81 No.11
<P>Hydrogen bonding is a vital feature of a large ensemble of chemical structures. Soluble epoxide hydrolase (sEH) has been targeted for development of the treatment for inflammation-associated diseases. Compounds <B>1</B> and <B>2</B> were purified from <I>Rubia philippinensis</I>, and their structures were established via physical data analysis. Compound <B>1</B> possesses intramolecular hydrogen bonding, sufficiently robust to transfer heteronuclear magnetization via a nonbonded interaction. The bonding strength was assessed using the <SUP>1</SUP>H NMR chemical shift temperature coefficients (−1.8 ppb/K), and the heteronuclear coupling constants were measured. The stereochemical details were investigated using interproton distance analysis and ECD. Purified compounds displayed moderate sEH-inhibitory activity.</P> [FIG OMISSION]</BR>