• Title, Summary, Keyword: H series inhibitor

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Isolation and Characterization of α-Glucosidase Inhibitor Produced by Bacillus sp. SKU31-1 Strain (Bacillus sp. SKU31-1가 생산하는 α-Glucosidase 저해제 분리 및 특성 조사)

  • Kim, Shin-Duk
    • Korean Journal of Microbiology
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    • v.50 no.4
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    • pp.381-383
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    • 2014
  • In the course of screening for ${\alpha}$-glucosidase inhibitor produced by microorganism, the active compound was isolated from the culture filtrate of Bacillus sp. SKU31-1 using a series of chromatography procedures. The structure of the active compound was elucidated as 5-amino-1-hydroxymethyl-1, 2, 3, 4-cyclohexanetetrol on the basis of spectroscopic evidence obtained and comparison with data from the literature. The active compound showed potent inhibitory activity against ${\alpha}$-glucosidase with an $IC_{50}$ value of $1.9{\mu}M$ for maltose and 4.9 mM for sucrose. A Lineweaver-Burk plot indicated that its inhibition of ${\alpha}$-glucosidase was competitive, with a $K_i$ value of 0.15 mM.

Synthesis and Biological Activity of New 4-(Pyridin-4-yl)-(3-methoxy-5-methylphenyl)-1H-pyrazoles Derivatives as ROS Receptor Tyrosine Kinase Inhibitors

  • Park, Byung Sun;El-Deeb, Ibrahim M.;Yoo, Kyung Ho;Han, Dong Keun;Tae, Jin Sung;Lee, So Ha
    • Bulletin of the Korean Chemical Society
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    • v.33 no.11
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    • pp.3629-3634
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    • 2012
  • A series of new 4-(pyridin-4-yl)-(3-methoxy-5-methylphenyl)-1H-pyrazoles (6a-k & 7a-l) has been rationally designed based on the structure of the lead compound KIST301080, a selective ROS receptor tyrosine kinase inhibitor, in order to study the activity of ROS of this new class of inhibitors. The compounds were synthesized and screened against ROS kinase, where compound 6h showed moderate inhibitory activity with an $IC_{50}$ value of $6.25{\mu}M$. The study emphasized the importance of the acetonitrile group at the pyrazole ring and also the importance of having a hydrogen bond donor on the distal phenyl ring linked to the pyridine moiety.

Solid-phase Synthesis and Preliminary Evaluation of 1,6,8-Trisubstituted Tetrahydro-2H-pyrazino[1,2-a]pyrimidine-4,7-diones as a NF-kB Inhibitor

  • Kim, Jin-Woong;Cho, Jung-Hyuck;Han, Tae-hee;Lee, Jong-Baek;Oh, Chang-Hyun
    • Bulletin of the Korean Chemical Society
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    • v.27 no.4
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    • pp.484-488
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    • 2006
  • The solid-phase synthesis of new series of 1,6,8-trisubstituted tetrahydro-2H-pyrazino[1,2-a]pyrimidine-4,7-diones as bicyclic $\beta$-turn mimetics is described. Their NF-kB inhibition activities were tested and the effect of substituents on bicyclic ring was investigated. Among the prepared compounds, the fluorobenzyl and methoxybenzyl group substituted compounds 26 and 27 at C-1 and C-8 position showed more inhibitory activities than the others. Tested at a concentration of 10 uM, these two compounds showed a 60% inhibition against the target NF kB 549.

Receptor-oriented Pharmacophore-based in silico Screening of Human Catechol O-Methyltransferase for the Design of Antiparkinsonian Drug

  • Lee, Jee-Young;Baek, Sun-Hee;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • v.28 no.3
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    • pp.379-385
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    • 2007
  • Receptor-oriented pharmacophore-based in silico screening is a powerful tool for rapidly screening large number of compounds for interactions with a given protein. Inhibition of the enzyme catechol-Omethyltransferase (COMT) offers a novel possibility for treating Parkinson's disease. Bisubstrate inhibitors of COMT containing the adenine of S-adenosylmethionine (SAM) and a catechol moiety are a new class of potent and selective inhibitor. In the present study, we used receptor-oriented pharmacophore-based in silico screening to examine the interactions between the active site of human COMT and bisubstrate inhibitors. We generated 20 pharmacophore maps, of which 4 maps reproduced the docking model of hCOMT and a bisubstrate inhibitor. Only one of these four, pharmacophore map I, effectively described the common features of a series of bisubstrate inhibitors. Pharmacophore map I consisted of one hydrogen bond acceptor (to Mg2+), three hydrogen bond donors (to Glu199, Glu90, and Gln120), and one hydrophobic feature (an active site region surrounded by several aromatic and hydrophobic residues). This map represented the most essential pharmacophore for explaining interactions between hCOMT and a bisubstrate inhibitor. These results revealed a pharmacophore that should help in the development of new drugs for treating Parkinson's disease.

G Protein Mediated Hatching Regulation in the Mouse Embryo

  • Cheon, Yong-Pil
    • Development and Reproduction
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    • v.16 no.1
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    • pp.69-75
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    • 2012
  • Hatching occurred in the time dependent manners and strictly controlled. Although, the hatching processes are under the control of muti-embryotrophic factors and the expressed G proteins of cell generate integrated activation, the knowledge which GPCRs are expressed during hatching stage embryos are very limited. In the present study, which G proteins are involved was examined during blastocyst development to the hatching stage. The early-, expanded-, and lobe-stage blastocysts were treated with various $G_{\alpha}$ activators and H series inhibitors, and examined developmental patterns. Pertusis toxin (PTX) improved the hatching rate of the early-stage blastocyst and lobe-formed embryos. Cholera toxin (CTX) suppressed the hatching of the early-stage blastocyst and expanded embryos. The effects of toxins on hatching and embryo development were changed by the H7 and H8. These results mean that PTX mediated GPCRs activation is signaling generator in the nick or pore formation in the ZP. In addition, PTX mediated GPCR activation induces the locomotion of trophectoderm for the escaping. CTX mediate GPCRs activation is the cause of suppression of hatching processes. Based on these data, it is suggested that various GPCRs are expressed in the periimplantation stage embryos and the integration of the multiple signals decoding of various signals in a spatial and temporal manner regulate the hatching process.

Topoisomerase I Inhibitors from the Streptomyces sp. Strain KM86-9B Isolated from a Marine Sponge

  • Lee, Hong-Kum;Lee, Deuk-Soo;Lim, Jung-Hyun;Kim, Jung-Sun;Im, Kwang-Sik;Jung, Jee H.
    • Archives of Pharmacal Research
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    • v.21 no.6
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    • pp.729-733
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    • 1998
  • The crude extract of Streptomyces sp. strain KM86-9B, isolated from a marine sponge, displayed significant inhibition on topoisomerase I activity. Investigation of the ca usative components by bioactivity-directed fractionation resulted in the isolation of a series of iso- and anteiso-fatty acids.

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A New Class of Selective COX-2 Inhibitor: Luotonin A Homologues and their Aza-analogues (새로운 계열의 선택적 COX-2 저해제: Luotonin A 동족체 및 그 질소 유도체)

  • Kim, Dong-Hyeon;Liang, Jing-Liu;Oh, Joon-Seok;Jahng, Yurng-Dong;Kim, Jin-Cheul;Hong, Tae-Gyun;Hwang, Nam-Kyung;Chung, Hwan-Ki;Kim, Yun-Kyung;Chang, Hyeun-Wook
    • YAKHAK HOEJI
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    • v.51 no.5
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    • pp.313-317
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    • 2007
  • A series of luotonin A homologues and their aza-analogues were prepared and evaluated their inhibitory activities on COX-1 and 2 as well as their selectivities on COX-2. The aza-analogue of dimethylene-bridged homologue of luotonin A, 3,3'-dimethylene-2-(1',8'-naphthyrid-2'-yl)-4(3H)-quinazolinone (2b), exhibited strongest inhibitory activity against COX-1 and COX-2 dependent phase of prostaglandin $D_2$ generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with an $IC_{50}$ of 39.3 and $1.89{\mu}M$, respectively. Selectivity of 2b on COX-2 over COX-1 was 21 which implied 2b can be a potential lead for the development of selective COX-2 inhibitor.

Comparison of Some 3-(Substituted-Benzylidene)-1, 3-Dihydro-Indolin Derivatives as Ligands of Tyrosine Kinase Based on Binding Mode Studies and Biological Assay

  • Olgen, Sureyya
    • Archives of Pharmacal Research
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    • v.29 no.11
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    • pp.1006-1017
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    • 2006
  • A series of 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one, 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione and 2, 2'-dithiobis 3-(substituted-benylidene)-1, 3-dihydro-indole derivatives was investigated as inhibitor of $p60^{c-Src}$tyrosine kinase by performing receptor docking studies and inhibitory activity toward tyrosine phosphorylation. Some compounds were shown to be docked at the site, where the selective inhibitor PP1 [1-tert-Butyl-3-p-tolyl-1H-pyrazolo[3,4-d]pyrimidine-4-yl-amine] was embedded at the enzyme active site. Evaluation of all compounds for the interactions with the parameters of lowest binding energy levels, capability of hydrogen bond formations and superimposibility on enzyme active site by docking studies, it can be assumed that 3-(substituted-benzylidene)-1, 3-dihydro-indolin-2-one and thione derivatives have better interaction with enzyme active site then 2, 2'-dithiobis 3-(substituted-benzylidene)-1, 3-dihydro indole derivatives. The test results for the inhibitory activity against tyrosine kinase by Elisa method revealed that 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione derivatives have more activity then 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one derivatives.

Synthesis, Urease and Acetylcholine Esterase Inhibition Activities of Some 1,4-Disubstituted Thiosemicarbazides and their 2,5-Disubstituted Thiadiazoles

  • Saleem, Muhammad;Rafiq, Muhammad;Hanif, Muhammad;Rama, Nasim Hasan;Seo, Sung-Yum;Lee, Ki-Hwan
    • Bulletin of the Korean Chemical Society
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    • v.33 no.8
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    • pp.2741-2747
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    • 2012
  • A new series of 2,5-disubstituted-1,3,4-thiadiazoles 6a-i was synthesized by overnight stirring various 1,4-disubstituted thiosemicarbazides 5a-i in polyphosphoric acid followed by neutralization. The structures of newly synthesized compounds 5a-i and 6a-i were characterized by IR, $^1H$ and $^{13}C$ NMR, elemental analysis and mass spectrometric studies. All the synthesized compounds were evaluated for their urease and acetylcholine esterase inhibition activities. Thiosemicarbazides 5a-i are found to possess excellent potential for urease inhibition, more than the standard drug. Thiosemicarbazides 5a-i are more potent urease inhibitor than their cyclic analogues thiadiazoles 6a-i. Almost all of the compounds are excellent inhibitors of acetylcholine esterase. The inhibition of acetylcholine esterase of compounds 5a, 5c, 5d, 5g, 5i, 6e, 6f, 6g, and 6i is much more than that of standard drug.