Minkyoung Kim

Electrical characteristics of pentacene-based thin film transistor with conducting poly(3,4-ethylenedioxythiophene) electrodes

This is a report on the fabrication and electrical characteristics of an all-organic-based thin film transistor that uses conducting poly(3,4-ethylenedioxythiophene) (PEDOT) as electrodes. The conducting PEDOT layers as source, drain, and gate electrodes were patterned by using photolithography. The poly(vinyl cinnamate) (PVCN) was spin coated and cross-linked as a gate insulator. The pentacene as an active layer was vapor deposited onto the PVCN layer. In order to compare the characteristics of the pentacene-based organic thin film transistor (OTFT) with PEDOT electrodes, we fabricated another pentacene-based OTFT using a Si-based pattern with Au electrodes. The electrical characteristics of the devices, such as charge carrier mobility (μ), threshold voltage (Vth), and on/off current ratio (Ion∕off), were measured from its current-voltage (I-V) characteristic curves. The μ, Vth, and Ion∕off of the pentacene-based OTFT with PEDOT electrodes were ∼2.3×10−3cm2∕Vs, 4V, and ∼100, respectively. We evaluated th...

Therapeutic Strategies for Metabolic Diseases: Small‐Molecule Diacylglycerol Acyltransferase (DGAT) Inhibitors

Metabolic diseases such as atherogenic dyslipidemia, hepatic steatosis, obesity, and type II diabetes are emerging as major global health problems. Acyl‐CoA:diacylglycerol acyltransferase (DGAT) is responsible for catalyzing the final reaction in the glycerol phosphate pathway of triglycerol synthesis. It has two isoforms, DGAT‐1 and DGAT‐2, which are widely expressed and present in white adipose tissue. DGAT‐1 is most highly expressed in the small intestine, whereas DGAT‐2 is primarily expressed in the liver. Therefore, the selective inhibition of DGAT‐1 has become an attractive target with growing potential for the treatment of obesity and type II diabetes. Furthermore, DGAT‐2 has been suggested as a new target for the treatment of DGAT‐2‐related liver diseases including hepatic steatosis, hepatic injury, and fibrosis. In view the discovery of drugs that target DGAT, herein we attempt to provide insight into the scope and further reasons for optimization of DGAT inhibitors.

Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors.

A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC(50)=4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level.

Discovery of novel (1S)-(-)-verbenone derivatives with anti-oxidant and anti-ischemic effects.

A series of novel (1S)-(-)-verbenone derivatives was synthesized bearing a 4-styryl scaffold. The synthesized compounds were tested for their anti-oxidant, anti-excitotoxic, and anti-ischemic activities. These derivatives significantly reduced oxygen-glucose deprivation-induced neuronal injury and N-methyl-D-aspartic acid-evoked excitotoxicity in cortical neurons. Furthermore, compound 3f was identified as a potent anti-ischemic agent in an in vitro ischemic model, potentially due to the inhibition of N-methyl-D-aspartic acid-evoked excitotoxicity and oxidative/nitrosative stress.

Discovery of indolyl acrylamide derivatives as human diacylglycerol acyltransferase-2 selective inhibitors

A series of indolyl acrylamide derivatives was synthesized as potential diacylglycerol acyltransferase (DGAT) inhibitors. Furfurylamine containing indolyl acrylamide derivative 5h exhibited the most potent DGAT inhibitory activity using microsomes prepared from rat liver. Further evaluation against human DGAT-1 and DGAT-2 identified indolyl acrylamide analogues as selective inhibitors against human DGAT-2. In addition, the most potent compound 5h inhibited triglyceride synthesis dose-dependently in HepG2 cell lines.

A facile synthetic route to diazepinone derivatives via ring closing metathesis and its application for human cytidine deaminase inhibitors

A variety of diazepinone derivatives were prepared from α-amino acids and amino alcohols by a new synthetic methodology based on ring closing metathesis as a key step. The diazepinones were coupled with ribose derivatives to afford novel diazepinone nucleosides. Among them, (4R)-1-ribosyl-4-methyl-3,4-dihydro-1H-1,3-diazepin-2(7H)-one (3) showed a potent inhibitory effect (K(i) = 145.97 ± 4.87 nM) against human cytidine deaminase.

Up-regulation of astroglial heme oxygenase-1 by a synthetic (S)-verbenone derivative LMT-335 ameliorates oxygen-glucose deprivation-evoked injury in cortical neurons.

Excessive generation of free radicals is regarded as a major detrimental factor in cerebral ischemic insults. Neurons are particularly vulnerable to oxidative stress due to their limited anti-oxidant capacity. As an important source of antioxidants in the brain, astroglia are now thought to be attractive targets for pharmacological interventions to reduce neuronal oxidative stress in ischemic stroke. In the present study, we synthesized a novel antioxidant, the (1S)-(-)-verbenone derivative LMT-335, and investigated its anti-ischemic activities. In rat cortical neuronal/glial co-cultures, LMT-335 significantly reduced oxygen-glucose deprivation (OGD)/reoxygenation (R)-induced neuronal injury. Although it did not inhibit N-methyl-d-aspartate-induced excitotoxicity, LMT-335 significantly reduced OGD/R-evoked intracellular oxidative stress. However, the oxygen radical absorbance capacity assay and 1,1-diphenyl-2-picrylhydrazyl assay showed that the free radical scavenging activities of LMT-335 were lower than those of trolox. Instead, LMT-335 significantly increased the astroglial expression of heme oxygenase-1 (HO-1), a well-known anti-oxidant stress protein, as evidenced by immunocytochemistry and immunoblot analyses. Moreover, a selective HO-1 inhibitor, tin protoporphyrin IX (SnPP), significantly blocked the anti-ischemic effect of LMT-335. The present findings indicate that LMT-335 exerts neuroprotective effects against OGD/R by up-regulation of HO-1 in astroglial cells. Our data suggest that astroglial HO-1 represents a potential therapeutic target for the treatment of ischemic stroke.

Methyl 3-(3-(4-(2,4,4-Trimethylpentan-2-yl)phenoxy)-propanamido)benzoate as a Novel and Dual Malate Dehydrogenase (MDH) 1/2 Inhibitor Targeting Cancer Metabolism

Previously, we reported a hypoxia-inducible factor (HIF)-1 inhibitor LW6 containing an (aryloxyacetylamino)benzoic acid moiety inhibits malate dehydrogenase 2 (MDH2) using a chemical biology approach. Structure-activity relationship studies on a series of (aryloxyacetylamino)benzoic acids identified selective MDH1, MDH2, and dual inhibitors, which were used to study the relationship between MDH enzyme activity and HIF-1 inhibition. We hypothesized that dual inhibition of MDH1 and MDH2 might be a powerful approach to target cancer metabolism and selected methyl-3-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propanamido)-benzoate (16c) as the most potent dual inhibitor. Kinetic studies revealed that compound 16c competitively inhibited MDH1 and MDH2. Compound 16c inhibited mitochondrial respiration and hypoxia-induced HIF-1α accumulation. In xenograft assays using HCT116 cells, compound 16c demonstrated significant in vivo antitumor efficacy. This finding provides concrete evidence that inhibition of both MDH1 and MDH2 may provide a valuable platform for developing novel therapeutics that target cancer metabolism and tumor growth.

Organic perylene single crystal based field-effect transistor

We report on the fabrication and characteristics of organic field-effect transistors (OFETs) using a single crystal of perylene. Perylene single crystals were relatively fast grown in furnace with flowing nitrogen gas. The OFETs were prepared by placing a perylene single crystal flake onto SiO2/Si or polymer insulator/Si substrates. The field-effect mobility of the perylene based OFETs temperature. was measured to be 1.6 times 10-4cm2 /Vs at room