Inhibition of secreted phospholipases A₂ by 2-oxoamides based on α-amino acids: Synthesis, in vitro evaluation and molecular docking calculations.

Abstract:

:Group IIA secreted phospholipase A₂ (GIIA sPLA₂) is a member of the mammalian sPLA₂ enzyme family and is associated with various inflammatory conditions. In this study, the synthesis of 2-oxoamides based on α-amino acids and the in vitro evaluation against three secreted sPLA₂s (GIIA, GV and GX) are described. The long chain 2-oxoamide GK126 based on the amino acid (S)-leucine displayed inhibition of human and mouse GIIA sPLA₂s (IC₅₀ 300nM and 180nM, respectively). It also inhibited human GV sPLA₂ with similar potency, while it did not inhibit human GX sPLA₂. The elucidation of the stereoelectronic characteristics that affect the in vitro activity of these compounds was achieved by using a combination of simulated annealing to sample low-energy conformations before the docking procedure, and molecular docking calculations.

journal_name

Bioorg Med Chem

authors

Mouchlis VD,Magrioti V,Barbayianni E,Cermak N,Oslund RC,Mavromoustakos TM,Gelb MH,Kokotos G

doi

10.1016/j.bmc.2010.12.030

subject

Has Abstract

pub_date

2011-01-15 00:00:00

pages

735-43

issue

2

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(10)01121-1

journal_volume

19

pub_type

杂志文章
  • A novel thrombin binding aptamer containing a G-LNA residue.

    abstract::In this work, we report the solution structure, thermodynamic studies, and the pharmacological properties of a new modified thrombin binding aptamer (TBA) containing a G-LNA residue, namely d(5'-GGTTGGTGTGGTTGg-3'), where upper case and lower case letters represent DNA and LNA residues, respectively. NMR and CD spectr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.06.008

    authors: Virno A,Randazzo A,Giancola C,Bucci M,Cirino G,Mayol L

    更新日期:2007-09-01 00:00:00

  • Syntheses and evaluation of antioxidant activity of sydnonyl substituted thiazolidinone and thiazoline derivatives.

    abstract::3-Aryl-4-formylsydnone 4'-phenylthiosemicarbazones (3a-d) and 3-aryl-4-formylsydnone thiosemicarbazones (3e-h), which are precursors of 3-aryl-4-heterocyclic sydnones, are prepared by the condensation of 3-aryl-4-formylsydnones (1a-d) with 4'-phenylthiosemicarbazide (2a) and thiosemicarbazide (2b), respectively. The t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.06.033

    authors: Shih MH,Ke FY

    更新日期:2004-09-01 00:00:00

  • 1,3,7-Triethyl-substituted xanthines--possess nanomolar affinity for the adenosine A1 receptor.

    abstract::Adenosine A1 receptors are attracting great interest as drug targets for their role in cognitive deficits. Antagonism of the adenosine A1 receptor may offer therapeutic benefits in complex neurological diseases, such as Alzheimer's and Parkinson's disease. The aim of this study was to discover potential selective aden...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.09.012

    authors: Van der Walt MM,Terre'Blanche G

    更新日期:2015-10-15 00:00:00

  • Homology modelling and active-site-mutagenesis study of the catalytic domain of the pneumococcal phosphorylcholine esterase.

    abstract::Streptococcus pneumoniae is among the major human pathogens. Several interactions of this bacterium with its host appear to have been mediated by bacterial cell wall components. Specifically, phosphorylcholine residues covalently attached to teichoic and lipoteichoic acids serve as anchors for many surface-located pro...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.06.060

    authors: Campillo NE,Páez JA,Lagartera L,Gonzalez A

    更新日期:2005-12-01 00:00:00

  • Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase.

    abstract::The first published synthesis and characterization of a purine-scaffold library of hsp90 inhibitors is presented. The purine-scaffold represents a platform for the creation of easily synthesizable and derivatizable soluble molecules that are amenable for oral administration. The most active compound of the series (71)...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00253-5

    authors: Chiosis G,Lucas B,Shtil A,Huezo H,Rosen N

    更新日期:2002-11-01 00:00:00

  • Model studies for isolation of G-quadruplex-forming DNA sequences through a pull-down strategy with macrocyclic polyoxazole.

    abstract::G-quadruplexes (G4s) are non-B DNA structures present in guanine-rich regions of gene regulatory areas, promoters and CpG islands, but their occurrence and functions remain incompletely understood. Thus, methodology to identify G4 sequences is needed. Here, we describe the synthesis of a novel cyclic hepta-oxazole com...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.02.056

    authors: Iida K,Tsushima Y,Ma Y,Sedghi Masoud S,Sakuma M,Yokoyama T,Yoshida W,Ikebukuro K,Nagasawa K

    更新日期:2019-04-15 00:00:00

  • Synthesis and antihyperglycemic activity of chalcone based aryloxypropanolamines.

    abstract::A series of aryloxypropanolamines (5a-r) of different chalcones (3a-e) were synthesized and evaluated for antihyperglycemic activity in sucrose loaded (SLM) and streptozotocin (STZ) induced diabetic animal models. Among them compounds 5a, g, m, o, p and r showed significant reduction in blood glucose levels in both SL...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2003.12.026

    authors: Satyanarayana M,Tiwari P,Tripathi BK,Srivastava AK,Pratap R

    更新日期:2004-03-01 00:00:00

  • Activation of lysine-specific demethylase 1 inhibitor peptide by redox-controlled cleavage of a traceless linker.

    abstract::We have previously employed cyclization of a linear peptide as a strategy to modulate peptide function and properties, but cleavage to regenerate the linear peptide left parts of the linker structure on the peptide, interfering with its activity. Here, we focused on cyclization of a linear peptide via a "traceless" di...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.12.033

    authors: Amano Y,Umezawa N,Sato S,Watanabe H,Umehara T,Higuchi T

    更新日期:2017-02-01 00:00:00

  • QSAR of the testosterone binding globulin affinity by means of correlation weighting of local invariants of the graph of atomic orbitals.

    abstract::Numerical values of the testosterone binding globulin affinity have been modeled as a mathematical function of molecular structure in two versions of molecular structure elucidation: first, by hydrogen-filled molecular graphs (HFG); second, by the so-called graphs of atomic orbitals (GAO). Increased orders of Morgan e...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.07.059

    authors: Raska I Jr,Toropov A

    更新日期:2005-12-15 00:00:00

  • Veratridine binding to a transmembrane helix of sodium channel Nav1.4 determined by solid-state NMR.

    abstract::The multi-step ligand action to a target protein is an important aspect when understanding mechanisms of ligand binding and discovering new drugs. However, structurally capturing such complex mechanisms is challenging. This is particularly true for interactions between large membrane proteins and small molecules. One ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.10.012

    authors: Niitsu A,Egawa A,Ikeda K,Tachibana K,Fujiwara T

    更新日期:2018-11-15 00:00:00

  • Combined NMR and molecular modeling study of an iduronic acid-containing trisaccharide related to antithrombotic heparin fragments.

    abstract::An iduronic acid-containing trisaccharide, methyl-O-(4-O-methyl-2,3,6-tri-O-sulfo-alpha-D-glucopyranosyl-(1-->4)-O- (2-O-sulfo-alpha-L-idopyranosyluronic acid)-(1-->4)-O-2,6-di-O-sulfo-alpha-D-glucopyranoside, related to antithrombotic heparin fragments has been subjected to a combined NMR and molecular modeling inves...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(97)00087-4

    authors: Cros S,Petitou M,Sizun P,Pérez S,Imberty A

    更新日期:1997-07-01 00:00:00

  • 2- and 3-substituted imidazo[1,2-a]pyrazines as inhibitors of bacterial type IV secretion.

    abstract::A novel series of 8-amino imidazo[1,2-a]pyrazine derivatives has been developed as inhibitors of the VirB11 ATPase HP0525, a key component of the bacterial type IV secretion system. A flexible synthetic route to both 2- and 3-aryl substituted regioisomers has been developed. The resulting series of imidazo[1,2-a]pyraz...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.09.036

    authors: Sayer JR,Walldén K,Pesnot T,Campbell F,Gane PJ,Simone M,Koss H,Buelens F,Boyle TP,Selwood DL,Waksman G,Tabor AB

    更新日期:2014-11-15 00:00:00

  • Design and synthesis of novel benzimidazole derivatives as inhibitors of hepatitis B virus.

    abstract::A series of novel benzimidazole derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in the HepG2.2.15 cell line. The preliminary SAR was discussed. Compound 12a, with IC50<0.41 microM and SI>81.2, was the most promising compound and selected as the benchmark comp...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.05.076

    authors: Luo Y,Yao JP,Yang L,Feng CL,Tang W,Wang GF,Zuo JP,Lu W

    更新日期:2010-07-15 00:00:00

  • Bromo-deaza-SAH: a potent and selective DOT1L inhibitor.

    abstract::Chemical inhibition of proteins involved in chromatin-mediated signaling is an emerging strategy to control chromatin compaction with the aim to reprogram expression networks to alter disease states. Protein methyltransferases constitute one of the protein families that participate in epigenetic control of gene expres...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.01.049

    authors: Yu W,Smil D,Li F,Tempel W,Fedorov O,Nguyen KT,Bolshan Y,Al-Awar R,Knapp S,Arrowsmith CH,Vedadi M,Brown PJ,Schapira M

    更新日期:2013-04-01 00:00:00

  • Enediyne-mediated cleavage of RNA.

    abstract::RNA cleavage by enediyne anticancer antibiotics was shown to occur with no apparent sequence selectivity, but RNA structure appears to be important in those substrates where cleavage was observed. Neocarzinostatin (NCS) cleaved a wider variety of RNA substrates than either esperamicin (ESP) or calicheamicin (CAL), and...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(95)00046-j

    authors: Battigello JM,Cui M,Roshong S,Carter BJ

    更新日期:1995-06-01 00:00:00

  • Actin-binding doliculide causes premature senescence in p53 wild type cells.

    abstract::Addressing the actin cytoskeleton as future anticancer target can be an innovative chemotherapeutic approach to combat malignancies. Doliculide is a potent stabilizer of actin filaments and can be used as tool and therapeutic lead in cancer research. Though a variety of molecules are known to bind to actin and lead to...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.11.042

    authors: Foerster F,Chen T,Altmann KH,Vollmar AM

    更新日期:2016-01-15 00:00:00

  • 2-Amino-4-methyl-5-phenylethyl substituted-7-N-benzyl-pyrrolo[2,3-d]pyrimidines as novel antitumor antimitotic agents that also reverse tumor resistance.

    abstract::Gangjee et al. recently reported a novel series of 2-amino-4-methyl-5-phenylethyl substituted-7-benzyl-pyrrolo[2,3-d]pyrimidines, some of which exhibited two digit nanomolar antitumor and antimitotic activity and were not subject to P-glycoprotein (Pgp) or multidrug resistance protein 1 (MRP1) mediated tumor resistanc...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.05.030

    authors: Gangjee A,Namjoshi OA,Keller SN,Smith CD

    更新日期:2011-07-15 00:00:00

  • Exploration of benzamidochromenone derivatives with conformational restrictor as interleukin-5 inhibitors.

    abstract::Novel amidochromen-4-one analogs 8a-k and 9a-f were prepared and studied for their IL-5 inhibitory activity. Among the synthesized compounds, (6-benzamido-2-cyclohexyl-4-oxo-4H-chromen-3-yl)methyl acetate (8a, 95% inhibition at 30 μM, IC50=6.1 μM) exhibited potent IL-5 inhibitory activity. The conformational restricto...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.03.045

    authors: Venkateswararao E,Manickam M,Boggu P,Kim Y,Jung SH

    更新日期:2015-05-15 00:00:00

  • Characterization, bioinformatic analysis and dithiocarbamate inhibition studies of two new α-carbonic anhydrases, CAH1 and CAH2, from the fruit fly Drosophila melanogaster.

    abstract::Carbonic anhydrases (CAs) are essential and ubiquitous enzymes. Thus far, there are no articles on characterization of Drosophila melanogaster α-CAs. Data from invertebrate CA studies may provide opportunities for anti-parasitic drug development because α-CAs are found in many parasite or parasite vector invertebrates...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.08.046

    authors: Syrjänen L,Tolvanen ME,Hilvo M,Vullo D,Carta F,Supuran CT,Parkkila S

    更新日期:2013-03-15 00:00:00

  • Synthesis and biochemical activity of novel amidine derivatives as m1 muscarinic receptor agonists.

    abstract::As part of a continuing effort aimed at the development of selective, efficacious, and centrally active m1 muscarinic agonists for the treatment of Alzheimer's disease, a series of amide and hydrazide amidine derivatives (2a-e and 3b-d) was synthesized and examined for muscarinic agonist activity. Preliminary biochemi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(96)00152-6

    authors: Ojo B,Dunbar PG,Durant GJ,Nagy PI,Huzl JJ 3rd,Periyasamy S,Ngur DO,el-Assadi AA,Hoss WP,Messer WS Jr

    更新日期:1996-10-01 00:00:00

  • NMR determination of Electrophorus electricus acetylcholinesterase inhibition and reactivation by neutral oximes.

    abstract::Neurotoxic organophosphorus compounds (OPs), which are used as pesticides and chemical warfare agents lead to more than 700,000 intoxications worldwide every year. The main target of OPs is the inhibition of acetylcholinesterase (AChE), an enzyme necessary for the control of the neurotransmitter acetylcholine (ACh). T...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.05.063

    authors: da Cunha Xavier Soares SF,Vieira AA,Delfino RT,Figueroa-Villar JD

    更新日期:2013-09-15 00:00:00

  • YM-254890 analogues, novel cyclic depsipeptides with Galpha(q/11) inhibitory activity from Chromobacterium sp. QS3666.

    abstract::The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.04.006

    authors: Taniguchi M,Suzumura K,Nagai K,Kawasaki T,Takasaki J,Sekiguchi M,Moritani Y,Saito T,Hayashi K,Fujita S,Tsukamoto S,Suzuki K

    更新日期:2004-06-15 00:00:00

  • 2-O-substituted cyclodextrins as reversal agents for the neuromuscular blocker rocuronium bromide.

    abstract::A series of secondary face modified cyclodextrins (CDs) were synthesised with the aim of constructing host molecules capable of forming host-guest complexes with neuromuscular blockers, especially with rocuronium bromide. Perfacial 2-O-substitution of gamma-CD with 4-carboxybenzyl resulted in a CD host molecule 1 that...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00026-3

    authors: Tarver GJ,Grove SJ,Buchanan K,Bom A,Cooke A,Rutherford SJ,Zhang MQ

    更新日期:2002-06-01 00:00:00

  • A novel non-stochastic quadratic fingerprints-based approach for the 'in silico' discovery of new antitrypanosomal compounds.

    abstract::A non-stochastic quadratic fingerprints-based approach is introduced to classify and design, in a rational way, new antitrypanosomal compounds. A data set of 153 organic chemicals, 62 with antitrypanosomal activity and 91 having other clinical uses, was processed by a k-means cluster analysis to design training and pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.06.049

    authors: Montero-Torres A,Vega MC,Marrero-Ponce Y,Rolón M,Gómez-Barrio A,Escario JA,Arán VJ,Martínez-Fernández AR,Meneses-Marcel A

    更新日期:2005-11-15 00:00:00

  • Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors.

    abstract::Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be less toxic than hydroxamate and are worthy of further consideration. Therefore, we have designed a series of analogs as potential inhibitors of HDACs, in which t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.12.005

    authors: Osada S,Sano S,Ueyama M,Chuman Y,Kodama H,Sakaguchi K

    更新日期:2010-01-15 00:00:00

  • Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist.

    abstract::Polyamines and polyamine toxins are biologically important molecules, having modulatory effects on nucleotides and proteins. The wasp toxin, philanthotoxin-433 (PhTX-433), is a non-selective and uncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine recepto...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.05.023

    authors: Andersen TF,Vogensen SB,Jensen LS,Knapp KM,Strømgaard K

    更新日期:2005-09-01 00:00:00

  • Exploring a synthetic organoselenium compound for antioxidant pharmacotherapy--toxicity and effects on ROS-production.

    abstract::The organoselenium antioxidant 1 was previously found to act as a catalytic antioxidant in a two-phase lipid peroxidation system. In aqueous environment, selenide 1 quenched ABTS-radicals more efficiently than Trolox and ascorbic acid. The selenide dose-dependently scavenged reactive oxygen and nitrogen species more e...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.01.057

    authors: Johansson H,Svartström O,Phadnis P,Engman L,Ott MK

    更新日期:2010-03-01 00:00:00

  • Synthesis, structure-affinity relationships, and modeling of AMDA analogs at 5-HT2A and H1 receptors: structural factors contributing to selectivity.

    abstract::Histamine H(1) and serotonin 5-HT(2A) receptors present in the CNS have been implicated in various neuropsychiatric disorders. 9-Aminomethyl-9,10-dihydroanthracene (AMDA), a conformationally constrained diarylalkyl amine derivative, has affinity for both of these receptors. A structure-affinity relationship (SAFIR) st...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.08.016

    authors: Shah JR,Mosier PD,Roth BL,Kellogg GE,Westkaemper RB

    更新日期:2009-09-15 00:00:00

  • Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (2).

    abstract::3-Metoxycarbonyl isoquinolone derivative 1 has been identified as a potent JNK inhibitor and significantly inhibited cardiac hypertrophy in a rat pressure-overload model. Herein, a series of isoquinolones with an imidazolylmethyl or a pyrazolylmethyl group at the 2-position were designed based on X-ray crystallographi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.02.028

    authors: Asano Y,Kitamura S,Ohra T,Itoh F,Kajino M,Tamura T,Kaneko M,Ikeda S,Igata H,Kawamoto T,Sogabe S,Matsumoto S,Tanaka T,Yamaguchi M,Kimura H,Fukumoto S

    更新日期:2008-04-15 00:00:00

  • Beta-hairpin and beta-sheet formation in designed linear peptides.

    abstract::Recent knowledge about the determinants of beta-sheet formation and stability has notably been improved by the structural analysis of model peptides with beta-hairpin structure in aqueous solution. Several experimental studies have shown that the turn region residues can not only determine the stability, but also the ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(98)00215-6

    authors: Ramírez-Alvarado M,Kortemme T,Blanco FJ,Serrano L

    更新日期:1999-01-01 00:00:00