Anthranilic acid based CCK1 receptor antagonists: Blocking the receptor with the same ‘words’ of the endogenous ligand

Lassiani, Lucia; Pavan, Michela V.; Berti, Federico; Kokotos, George; Markidis, Theodoros; Mennuni, Laura; Makovec, Francesco; Varnavas, Antonio

doi:10.1016/j.bmc.2009.02.012

Cited by 13 publications

(10 citation statements)

References 38 publications

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“…Anthranilic acid derivatives have been recognized to have diverse biological activities, [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] in particular, they are enzymatic inhibitors of VEGF receptor kinase, 14 matrix metalloproteinase (MMP), 15 acyl carrier protein synthase (AcpS), 16 methionine aminopeptidase-2, 17,18 phospholipase A 2 , 19 human hydroxysteroid dehydrogenase AKR1C1, 20 plasminogen activator inhibitor-1, 21 and cholecystokinin (CCK). [22][23][24] In addition, they also exhibit anti-cancer, anti-hepatitis C virus (anti-HCV), anti-Alzheimer, anti-inflammatory, anti-platelet, and anti-bacterial activities. [25][26][27][28][29][30][31][32][33][34][35] Of these, the N-phenylanthranilic acids, e.g.…”

Section: Introductionmentioning

confidence: 99%

Anthranilic acid-based inhibitors of phosphodiesterase: Design, synthesis, and bioactive evaluation

et al. 2011

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Our previous studies identified two 2-benzoylaminobenzoate derivatives 1, which potently inhibited superoxide (O(2)˙(-)) generation induced by formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) in human neutrophils. In an attempt to improve their activities, a series of anthranilic acid derivatives were synthesized and their anti-inflammatory effects and underlying mechanisms were investigated in human neutrophils. Of these, compounds 17, 18, 46, 49, and 50 showed the most potent inhibitory effect on FMLP-induced release of O(2)˙(-) in human neutrophils with IC(50) values of 0.20, 0.16, 0.15, 0.06, and 0.29 μM, respectively. SAR analysis showed that the activities of most compounds were dependent on the ester chain length in the A ring. Conversely, a change in the linker between the A and B ring from amide to sulfonamide or N-methyl amide, as well as exchanges in the benzene rings (A or B rings) by isosteric replacements were unfavorable. Further studies indicated that inhibition of O(2)˙(-) production in human neutrophils by these anthranilic acids was associated with an elevation in cellular cAMP levels through the selective inhibition of phosphodiesterase 4. Compound 49 could be approved as a lead for the development of new drugs in the treatment of neutrophilic inflammatory diseases.

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Section: Introductionmentioning

confidence: 99%

Anthranilic acid-based inhibitors of phosphodiesterase: Design, synthesis, and bioactive evaluation

et al. 2011

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“…The synthetic anti-convulsive and anti-nociceptive N -salicyloyltryptamine (STP), which also contains the benzoyltryptamine fragment found in compound 1 , was shown to reverse several redox and inflammatory parameters induced by LPS in Raw264.7 cells [38], though it had no effect on nitrite accumulation. A close analogue of compound 1 , containing an amide linkage instead of an oxalamide bridge, was reported as an antagonist of the CCK1 receptor [39]. To our knowledge, no biological activity of compound 1 has been reported in the literature.…”

Section: Discussionmentioning

confidence: 95%

Discovery of a Natural Product-Like iNOS Inhibitor by Molecular Docking with Potential Neuroprotective Effects In Vivo

et al. 2014

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In this study, we applied structure-based virtual screening techniques to identify natural product or natural product-like inhibitors of iNOS. The iNOS inhibitory activity of the hit compounds was characterized using cellular assays and an in vivo zebrafish larvae model. The natural product-like compound 1 inhibited NO production in LPS-stimulated Raw264.7 macrophages, without exerting cytotoxic effects on the cells. Significantly, compound 1 was able to reverse MPTP-induced locomotion deficiency and neurotoxicity in an in vivo zebrafish larval model. Hence, compound 1 could be considered as a scaffold for the further development of iNOS inhibitors for potential anti-inflammatory or anti-neurodegenerative applications.

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“…Analysis of the research data [1][2][3][4][5][6][7][8][9][10][11] indicates the widespread use of derivatives of N-phenylanthranilic acids in medicine, pharmacy, industry and various fields of science. N-phenylanthranilic acids derivatives have a wide synthetic and pharmacological potential [1][2][3][8][9][10][11]. The circumstances above caused the necessity to carry out the synthesis of new 4,5dymethoxy-N-(2´-carboxyphenyl)anthranilic acids, study of their reactivity and biological activity.…”

Section: Issn 2308-8303mentioning

confidence: 99%

Reactivity of phenylanthranilic acids derivatives. Xxiii. Synthesis and acid-base properties of 4,5-dymethoxy-n-(2´-carboxyphenyl)anthranilic acids

Isaev¹,

Sviechnikova²,

Devyatkina³

et al. 2013

J. org. pharm. chem.

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Anthranilic acid based CCK1 receptor antagonists: Blocking the receptor with the same ‘words’ of the endogenous ligand

Cited by 13 publications

References 38 publications

Anthranilic acid-based inhibitors of phosphodiesterase: Design, synthesis, and bioactive evaluation

Anthranilic acid-based inhibitors of phosphodiesterase: Design, synthesis, and bioactive evaluation

Discovery of a Natural Product-Like iNOS Inhibitor by Molecular Docking with Potential Neuroprotective Effects In Vivo

Reactivity of phenylanthranilic acids derivatives. Xxiii. Synthesis and acid-base properties of 4,5-dymethoxy-n-(2´-carboxyphenyl)anthranilic acids

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