Heesoon Lee

Visible photoluminescence from self-assembled InAs quantum dots embedded in AlAs cladding layers

Photoluminescence (PL) from InAs self-assembled quantum dots (QD) embedded in the AlAs matrix was strong and clean around 700 nm. PL efficiency remained quite high at room temperature compared to other QD systems embedded in GaAs cladding layers. Transmission electron microscope pictures from the structure showed a clear formation of relatively small and coherently strained InAs QD. The observed blueshift with accompanying broadening of PL spectra with the increase of excitation power is interpreted in terms of local carrier tunneling in a dense QD system. The PL peak redshift with the increase of temperature was very large, as much as 228 meV. The anomalous shift is interpreted as due to activation-energy differences between dots of different sizes.

Benzoxathiole Derivative Blocks Lipopolysaccharide-Induced Nuclear Factor-κB Activation and Nuclear Factor-κB-Regulated Gene Transcription through Inactivating Inhibitory κB Kinase β

Benzoxathiole derivatives have been used in the treatment of acne and have shown cytostatic, antipsoriatic, and antibacterial properties. However, little is known about the molecular basis for these pharmacological properties, although nuclear factor (NF)-κB activation is closely linked to inflammation and cell proliferation. Here, we demonstrate that the novel small-molecule benzoxathiole 6,6-dimethyl-2-(phenylimino)-6,7-dihydro-5H-benzo-[1,3]oxathiol-4-one (BOT-64) inhibits NF-κB activation with an IC50 value of 1 μM by blocking inhibitory κB(IκB) kinase β (IKKβ), and suppresses NF-κB-regulated expression of inflammatory genes in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. BOT-64 inhibits IKKβ-mediated IκBα phosphorylation in LPS-activated macrophages, resulting in sequential prevention of downstream events, including proteolytic degradation of IκBα, DNA binding ability, and transcriptional activity of NF-κB. BOT-64 inhibits LPS-inducible IKKβ activity in the cells and catalytic activity of highly purified IKKβ. Moreover, the effect of BOT-64 on cell-free IKKβ was abolished by substitution of Ser-177 and Ser-181 residues in the activation loop of IKKβ to glutamic acid residues, indicating a direct interaction site of benzoxathiole. BOT-64 attenuates NF-κB-regulated expression of inflammatory genes such as inducible nitric-oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in LPS-activated or expression vector IKKβ-transfected macrophages. Furthermore, BOT-64 dose-dependently increases the survival rates of endotoxin LPS-shocked mice.

Nuclear factor-kappa B inhibitors; a patent review (2006 – 2010)

Introduction: Nuclear factor (NF)-κB, as transcription factor, is linked to the expression of various genes and plays an essential role in immune and inflammatory responses. Abnormal NF-κB signaling results in human diseases, such as immune disorders, inflammation and various cancers. Therefore, regulation of NF-κB may treat or improve the symptoms in human disorders. Areas covered: This review provides information on recent NF-κB inhibitor-related patents from 2006 to 2010. The patents are explained and categorized by mechanism. The reader will gain an understanding of NF-κB function and the structure and biological activity of recently developed NF-κB inhibitors that may be new drug candidates. Expert opinion: NF-κB plays an essential role in the human body and thus regulation of NF-κB is very important for the treatment of diseases. Furthermore, patented compounds and peptides are available as lead compounds in drug development studies.

A new anti-inflammatory agent KL-1037 represses proinflammatory cytokine and inducible nitric oxide synthase (iNOS) gene expression in activated microglia

Excessive proinflammatory cytokine and NO production by activated microglia play a role in neurodegenerative disorders. In this study, we found that a new compound KL-1037 suppressed LPS-induced NO release/inducible nitric oxide synthase expression in BV2 mouse microglial cells. In addition, KL-1037 prominently diminished LPS-induced production of pro-inflammatory cytokines such as TNF-alpha, IL-1 beta and IL-6, while it increased anti-inflammatory IL-10 and TGF-beta 1 production. By RNase protection assay and RT-PCR, we showed that KL-1037 regulated iNOS and cytokines at transcriptional or post-transcriptional level. Further analysis of molecular mechanisms revealed that KL-1037 prominently increased intracellular cAMP levels and potentiated LPS-induced pCREB expression. However, LPS-induced MAP kinase or NF-kappa B activities were slightly or little changed by KL-1037. Treatment with cAMP antagonist or IL-10 neutralizing antibody completely reversed upregulation of IL-10 and partially repression of TNF-alpha or NO induced by KL-1037. These data suggest that microglial inactivation by KL-1037 is at least in part due to activation of PKA pathway and/or upregulation of IL-10. Thus, repressing proinflammatory cytokines and iNOS gene expression in activated microglia by KL-1037 may provide potential therapeutic strategies for various neurodegenerative diseases including ischemic cerebral disease.

ent-Kaurane Diterpenoids from Isodon japonicus

Five ent-kaurane diterpenoids, 6beta,7beta,14beta-trihydroxy-1alpha,19-diacetoxy-7alpha,20-epoxy- ent-kaur-16-en-15-one (1), 1alpha,6beta,7beta-trihydroxy-11alpha,19-diacetoxy-7alpha,20-epoxy-ent-kaur-16-en-15-one (2), 6-hydroxy-1alpha,19-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide (3), 19-hydroxy-1alpha,6-diacetoxy-6,7-seco- ent-kaur-16-en-15-one-7,20-olide (4), and 6-aldehyde-1alpha,19-diacetoxy-6,7-seco- ent-kaur-16-en-15-one-7,20-olide (5), along with 10 known ent-kaurane diterpenoids, pseurata C (6), longikaurin C (7), effusanin C (8), longikaurin B (9), longikaurin D (10), effusanin D (11), excisanin B (12), lasiokaurin (13), megathyrin A (14), and loxothyrin A (15), were isolated from the aerial parts of Isodon japonicus. Their structures were determined on the basis of spectroscopic (1D-, 2D-NMR and MS) and chemical evidence. The isolates were evaluated for their inhibitory effects on LPS-induced production of nitric oxide in murine macrophage RAW264.7 cells.

Synthesis and in vitro evaluation of 3-substituted-1-azaanthraquinones

Abstract In the course of developing novel antitumor agents, we synthesized 3-substituted-1-azaanthraquinones, incorporating the alkylating or latent alkylating substituents as potential antitumor agents. The most active comound 4 exhibited cytotoxic activity comparable to that of doxorubicin. The compounds 3–8 retained much of their activity against the doxorubicin-resistant cell line (MCF7/R).

Synthesis and antitumor activity of 7-substituted 20(RS)-camptothecin analogues

Novel water-soluble camptothecin analogues with excellent antitumor activity have been designed and synthesized by total synthesis. The analogues were evaluated for cytotoxic activity against five tumor cell lines. The most potent analogue 6c exhibited significant antitumor activity at wider range of doses as compared with camptothecin (T/C 243 % at 70mg/kg; T/C > 150% at 8.75–140mg/kg).

Synthesis of 7-hydroxy-4-oxo-4H-chromene-and 7-hydroxychroman-2-carboxylic acidN-alkyl amides and their antioxidant activities

A series of 7-hydroxy-4-oxo-4H-chromene- (3a - h) and 7-hydroxychroman-2-carboxylic acid N-alkyl amides (4a - g) were synthesized and their antioxidant activities were evaluated. While compounds 3a - h were less active, compounds 4a - g exhibited more potent inhibition of lipid peroxidation initiated by Fe2+ and ascorbic acid in rat brain homogenates. Among them, 7-hydroxychroman-2-carboxylic acid N-alkylamides (4e - g) bearing nonyl, decyl, and undecyl side chain exhibited 3 times more potent inhibition than trolox (1).

Design and synthesis of 3,4-dihydro-2H-benzo[h]chromene derivatives as potential NF-κB inhibitors

A novel class of NF-κB inhibitors were designed and synthesized based on KL-1156 (6-hydroxy-7-methoxychroman-2-carboxylic acid phenyl amide) which is unambiguously considered to be a promising inhibitor for the translocation step of NF-κB. Especially in this study we focused on the modifying the chroman moiety of KL-1156 into four parts for exploring the SAR studies linked with physical properties of substituents resulted the development of novel 1a-k, 2a-f, 3a-d and 4a-d derivatives of 3,4-dihydro-2H-benzo[h]chromene. From the SAR studies we were very delightfully identified that several new N-aryl-3,4-dihydro-2H-benzo[h]chromene-2-carboxamide derivatives (1a-k) exhibited good inhibitory activity and anti-proliferative activity than parent lead compound KL-1156, among them 1i exhibited outstanding inhibitory effect on LPS-induced NF-κB transcriptional activity and anti-proliferative activity on NCI-H23 lung cancer cell lines than KL-1156.

Synthesis and in vitro cytotoxicity of C(20)(RS)-camptothecin analogues modified at both B (or A) and E ring

A series of C(7) and C(20)-substituted camptothecin derivatives (12-14, 16-18) are prepared. Their syntheses and in vitro cytotoxicities are reported.