Specific Nonpeptide Inhibitors of Puromycin‐Sensitive Aminopeptidase with a 2,4(1H,3H)‐Quinazolinedione Skeleton.

Kakuta, Hiroki; Tanatani, Aya; Nagasawa, Kazuo; Hashimoto, Yuichi

doi:10.1002/chin.200415142

Cited by 3 publications

(3 citation statements)

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“…The synthesis of the target ligands 9a − i , 10a − f , and 15a − c was achieved in reasonable (unoptimized) yields and high purity, suitable for biological analysis. The synthesis of the 2-substituted target ligands was, however, not achieved by this methodology, unexpectedly leading instead to the quinazoline dione compounds 8a − f (see the Supporting Information, structure confirmed by IR spectroscopy − ). Alternative synthetic strategies were considered for the synthesis of the 2-subtituted targets.…”

Section: Discussionmentioning

confidence: 99%

Rational Design of Substituted Diarylureas: A Scaffold for Binding to G-Quadruplex Motifs

et al. 2008

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The design and synthesis of a series of urea-based non-polycyclic aromatic ligands with alkylaminoanilino side chains as telomeric and genomic G-quadruplex DNA interacting agents is described. Their interactions with quadruplexes have been examined by means of Fluorescent Resonance Energy Transfer melting, circular dichroism and surface plasmon resonance-based assays. These validate the design concept for such urea-based ligands and also show that they have significant selectivity for compared to duplex DNA, as well as for particular G-quadruplexes. The ligand-quadruplex complexes were investigated by computational molecular modeling, providing further information on structure activity relationships. Preliminary biological studies using short-term cell growth inhibition assays show that some of the ligands have cancer cell selectivity, although they appear to have low potency for intracellular telomeric G-quadruplex structures, suggesting that their cellular targets may be other, possibly oncogene-related quadruplexes.

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Section: Discussionmentioning

confidence: 99%

Rational Design of Substituted Diarylureas: A Scaffold for Binding to G-Quadruplex Motifs

et al. 2008

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“…40 (for review) Moreover, molecules with a broad spectrum of action such as KCN, NaN 3 , ammonium oxalate, N-ethyl-maleimide, and 8-hydroxyquinoline inhibit APN/CD13. 40 (for review) APN activity is also inhibited by puromycin (1), 74,75 lapstatin (2), 76 some N-phenylphthalimide derivatives such as compound 3, 77-80 several N-phenylhomophthalimide derivatives like PIQ-22 (4) 77,78 which has later been described as a rather puromycin-sensitive aminopeptidase (PSA) inhibitor by the same group, [80][81][82][83] phosphinate dipeptide analogues illustrated by hPheP[CH 2 ]Tyr (5), 84 pseudoglutamyl aminophosphinic peptides such as GluC(PO 2 CH 2 )Leu-Ala (6), 85 several variously substituted 3-amino-2-oxobutyramide exemplified by compound 7, 86 a-aminoboronic derivatives such as the benzyl derivative 8, 87 or a-aminobenzaldehydes illustrated by (S) 2-amino-5methylpentanal (9). 88 An eclectic set of compounds has been described and used for the biochemical characterization or/and inhibition of other proteases-e.g.…”

Section: A P N / C D 1 I N H I B I T O R Smentioning

confidence: 99%

Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects

Bauvois¹,

Dauzonne²

2005

Med. Res. Rev.

237

162

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Aminopeptidase N (APN)/CD13 (EC 3.4.11.2) is a transmembrane protease present in a wide variety of human tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). APN/CD13 expression is dysregulated in inflammatory diseases and in cancers (solid and hematologic tumors). APN/CD13 serves as a receptor for coronaviruses. Natural and synthetic inhibitors of APN activity have been characterized. These inhibitors have revealed that APN is able to modulate bioactive peptide responses (pain management, vasopressin release) and to influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis). Therefore, inhibition of APN/CD13 may lead to the development of anti-cancer and anti-inflammatory drugs. This review provides an update on the biological and pharmacological profiles of known natural and synthetic APN inhibitors. Current status on their potential use as therapeutic agents is discussed with regard to toxicity and specificity.

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“…Various literatures report numerous 2,4(1H,3H)quinazolinedione analogues showing a wide variety of biological activities such as anticancer [7][8][9][10][11][12][13][14][15][16][17][18][19][20], antimicrobial [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], antihypertensive [38][39][40], anticonvulsant [41][42][43][44][45][46][47][48][49], anti-inflammatory [50], 5-hydroxytryptamine 3 (5-HT 3 ) receptor antagonist [51], phosphodiesterase (PDE) 4 inhibition [52,53], calcium-independent phosphodiesterase enzyme inhibition (CaIPDE) [54], cyclin-dependent kinase 5 (CDK5) inhibition…”

Section: Introductionmentioning

confidence: 99%

A Series of 2,4(1H,3H)-Quinazolinedione Derivatives: Synthesis and Biological Evaluation as Potential Anticancer Agents

Akgün¹,

Yilmaz²,

Cetin-Atalay³

et al. 2015

LDDD

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A series of 6,7-disubstituted-3-{2-[4-(substituted)piperazin-1-yl]-2-oxoethyl}quinazoline-2,4(1H,3H)-dione derivatives (7-34) were synthesized and their structures were elucidated on the basis of analytical and spectral (UV, IR, 1 H-NMR, 13 C-NMR and MS) data. These synthesized compounds were evaluated for their in vitro cytotoxicities against a panel of three human cancer cell lines. According to the cytotoxicity screening results, 3-{2-[4-(4-chlorobenzyl)piperazin-1-yl]-2-oxoethyl} quinazoline-2,4(1H,3H)-dione (7) presented the highest activity against HUH-7, MCF-7 and HCT-116 cell line with the IC 50 values of 2.5, 6.8 and 4.9 µM, respectively.

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Specific Nonpeptide Inhibitors of Puromycin‐Sensitive Aminopeptidase with a 2,4(1H,3H)‐Quinazolinedione Skeleton.

Abstract: a 2,4(1H,3H)-Quinazolinedione Skeleton. -The title compound (III) and its derivatives (V) inhibit puromycin-sensitive amino-peptidase in a non-competitive manner. -(KAKUTA, H.; TANATANI, A.; NAGASAWA, K.; HASHIMOTO*, Y.; Chem.

Cited by 3 publications

References 1 publication

Rational Design of Substituted Diarylureas: A Scaffold for Binding to G-Quadruplex Motifs

Rational Design of Substituted Diarylureas: A Scaffold for Binding to G-Quadruplex Motifs

Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects

A Series of 2,4(1H,3H)-Quinazolinedione Derivatives: Synthesis and Biological Evaluation as Potential Anticancer Agents

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