Anthranilic acid derivatives: a new class of non-peptide CCK1 receptor antagonists

Varnavas, Antonio; Lassiani, Lucia; Valenta, Valentina; Berti, Federico; Mennuni, Laura; Makovec, Francesco

doi:10.1016/s0968-0896(02)00475-3

Cited by 20 publications

(20 citation statements)

References 30 publications

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“…Cyclopeptides with an anthranilic acid unit are rare in nature. Two antifungal cyclopeptides with an anthranilic acid unit, sclerotides A and B, were isolated from the marine-derived Aspergillus sclerotiorum PT06-1 in a nutrient-limited hypersaline cultural medium [11]. Anthranilic acid dimers with micromolar affinity for the CCK1 receptors were considered to be an important molecular scaffold in medicinal chemistry [12].…”

Section: Introductionmentioning

confidence: 99%

Two Novel Hepatocellular Carcinoma Cycle Inhibitory Cyclodepsipeptides from a Hydrothermal Vent Crab-Associated Fungus Aspergillus clavatus C2WU

Jiang

Chen

et al. 2013

Marine Drugs

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Two novel cyclodepsipeptides containing an unusual anthranilic acid dimer and a d-phenyllactic acid residues, clavatustides A (1) and B (2), were identified from cultured mycelia and broth of Aspergillus clavatus C2WU isolated from Xenograpsus testudinatus, which lives at extreme, toxic habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. This is the first example of cyclopeptides containing an anthranilic acid dimer in natural products, and the first report of microbial secondary metabolites from the hydrothermal vent crab. Clavatustides A (1) and B (2) suppressed the proliferation of hepatocellular carcinoma (HCC) cell lines (HepG2, SMMC-7721 and Bel-7402) in a dose-dependent manner, and induced an accumulation of HepG2 cells in G1 phase and reduction of cells in S phase.

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Section: Introductionmentioning

confidence: 99%

Two Novel Hepatocellular Carcinoma Cycle Inhibitory Cyclodepsipeptides from a Hydrothermal Vent Crab-Associated Fungus Aspergillus clavatus C2WU

Jiang

Chen

et al. 2013

Marine Drugs

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“…Attempts to simplify these compounds resulted in monomeric anthranilic acid derivatives, such as compound 25 (VL-0395), Fig. (4), endowed with submicromolar affinity towards CCK1R and a quite good selectivity [53,54]. The antagonist nature of this compound was confirmed by the inhibition of the guinea pig gallbladder contraction induced by CCK-8 in vivo, with a potency (ED 50 = 0.38 μmol/kg) similar to that exhibited by loxiglumide in the same assay.…”

Section: Anthranilic Acid Derivativesmentioning

confidence: 99%

Strategies for Design of Non Peptide CCK1R Agonist/Antagonist Ligands

García-López¹,

González‐Muñiz²,

Martı́n-Martı́nez³

et al. 2007

CTMC

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This review mainly covers last five year literature on CCK1R agonists and antagonists. These CCK1R ligands have been found following the two usual and complementary strategies for drug discovery: rational design based on structure activity relationships on the CCK-7 and CCK-4 peptide sequences of the endogenous ligands and random screening of diverse compounds, followed by hit optimization. The first group includes: chimeric bifunctional opioid/CCK peptides, designed as opioid agonists with balanced CCK1R/CCK2R antagonist activity for the treatment of neuropathic pain, antagonist and agonist dipeptoids, and 1,3-dioxoperhydropyrido[1,2-c]pyrimidine- and anthranilic acid-based antagonists. Among the ligands derived from random screening, a few new 1,4-benzodiazepine-, 1,5-benzodiazepine-, and five member ring heterocycle-based CCK1R ligands have been reported. Finally, taking into account the importance of receptor mapping studies for ligand optimization and future precise de novo receptor structure-based design of new selective and more effective ligands, the most significant conclusions of these studies have also been reviewed.

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“…4), prepared from 2, have been shown to inhibit matrix metalloproteinases (MMPs), enzymes that play a role in the remodelling in degradation of extracellular matrix proteins and have been implicated in the etiology of several diseases such as rheumatoid arthritis and cancer [139]. The amides 31 have been shown to be good CCK 1 (cholecystokinin, an endocrine and nervous system cellular messenger) receptor antagonists (R=carboxygroup-spacer -indolyl/naphtyl) [140]. Compounds of a similar structure, i.e.…”

Section: The Medicinal Chemistry Of Anthranilic Acidmentioning

confidence: 99%