3-Aminocoumarin

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase.[Pubmed:30410615]

Beilstein J Org Chem. 2018 Oct 2;14:2545-2552.

A series of 3-amino-6,7-dimethoxycoumarins conjugated with the N-benzylpyridinium moiety through an amide-bond linkage was synthesized and evaluated for their acetylcholinesterase inhibitory activity. A number of the benzylpyridinium derivatives exhibited potent activities with inhibitory concentration (IC50) values in the nanomolar concentration range. Among them, the 2,3-difluorobenzylpyridinium-containing compound was the most potent inhibitor with an IC50 value of 1.53 +/- 0.01 nM. Docking studies revealed that the synthesized compounds inhibit the target enzyme by a dual binding site mechanism whereby the coumarin portion binds with the peripheral anionic site while the N-benzylpyridinium residue binds with the catalytic anionic site of the enzyme.

A diastereoselective synthesis of tetrahydro- and dihydro-pyrido[2,3-c]coumarin derivatives via a one-pot three-component Povarov reaction catalyzed by bismuth(III) chloride.[Pubmed:27624077]

Bioorg Med Chem Lett. 2016 Oct 15;26(20):5119-5125.

A diastereoselective synthesis of tetrahydro- and dihydro-pyrido[2,3-c]coumarin derivatives has been achieved via a one-pot three-component aza-Diels-Alder reaction of aromatic aldehydes, 3-Aminocoumarin and dienophiles catalyzed by BiCl3. NOE studies proved that exo-isomers were obtained in all cases with high selectivity. The reaction proceeded at room temperature providing good yields of products as well as applicability on a wide range of substrates. Among all the synthesized derivatives, compounds 4i and 4k showed promising DPPH radical scavenging activity as compared to other tested derivatives.

Antimicrobial and antioxidant activities of new metal complexes derived from 3-aminocoumarin.[Pubmed:21844844]

Molecules. 2011 Aug 15;16(8):6969-84.

3-Aminocoumarin (L) has been synthesized and used as a ligand for the formation of Cr(III), Ni(II), and Cu(II) complexes. The chemical structures were characterized using different spectroscopic methods. The elemental analyses revealed that the complexes where M=Ni(II) and Cu(II) have the general formulae [ML(2)Cl(2)], while the Cr(III) complex has the formula [CrL(2)Cl(2)]Cl. The molar conductance data reveal that all the metal chelates, except the Cr(III) one, are non-electrolytes. From the magnetic and UV-Visible spectra, it is found that these complexes have octahedral structures. The stability for the prepared complexes was studied theoretically using Density Function Theory. The total energy for the complexes was calculated and it was shown that the copper complex is the most stable one. Complexes were tested against selected types of microbial organisms and showed significant activities. The free radical scavenging activity of metal complexes have been determined by measuring their interaction with the stable free radical DPPH and all the compounds have shown encouraging antioxidant activities.

Povarov reactions involving 3-aminocoumarins: synthesis of 1,2,3,4-tetrahydropyrido[2,3-c]coumarins and pyrido[2,3-c]coumarins.[Pubmed:18821803]

J Org Chem. 2008 Nov 7;73(21):8437-47.

Condensation of 3-Aminocoumarin (5) with 4-nitrobenzaldehyde (8) afforded a 2-azadiene (9), which reacted with various electron-rich alkenes (10 examples) in the presence of Yb(OTf)3 to afford 1,2,3,4-tetrahydropyrido[2,3-c]coumarins. Yields were generally good, but the diastereomeric ratios were highly variable. The products arose through a formal [4 + 2] cycloaddition (inverse electron demand Diels-Alder reaction) followed by tautomerization. As such, these are examples of the Povarov reaction. A range of 1,2,3,4-tetrahydropyrido[2,3-c]coumarins was then synthesized using a three-component version of this reaction, which involves in situ formation of the 2-azadiene component. Some of these products were converted into the corresponding pyrido[2,3-c]coumarins upon treatment with various oxidants, the most effective of which proved to be nitrous gases.

New novobiocin analogues as antiproliferative agents in breast cancer cells and potential inhibitors of heat shock protein 90.[Pubmed:17979263]

J Med Chem. 2007 Nov 29;50(24):6189-200.

Selective hsp90 inhibitors simultaneously destabilize and deplete key signaling proteins involved in cell proliferation and survival, angiogenesis, and metastasis. Investigation of novobiocin analogues lacking the noviose moiety as novel inhibitors of hsp90 was carried out. A novel series of 3-Aminocoumarin analogues has been produced and screened in cell proliferation, and the molecular signature of hsp90 inhibition was assessed by depletion of estrogen receptor, HER2, Raf-1, and cdk4 in human breast cancer cells. This structure-activity relationship study highlights the crucial role of the C-4 and/or C-7 positions of coumarin which appeared to be essential for degradation of hsp90 client proteins. Removal of the noviose moiety in novobiocin together with introduction of a tosyl substituent at C-4 or C-7 coumarins provides 6e and 6f as lead structures which compared favorably with novobiocin as demonstrated by enhanced rates of cell death. The processing and activation of caspases 7 and 8 and the subsequent cleavage of PARP by 6e suggest stimulation of the extrinsic apoptosis pathway.

Antifeeding and insect-growth-regulating activity of certain metal complexes towards Spodoptera litura; F.[Pubmed:1392468]

Biometals. 1992 Spring;5(1):23-7.

Metal complexes of divalent cobalt, nickel and copper and trivalent iron were synthesized using N-salicylidene-3-Aminocoumarin as chelating agent. The ligand behaves as a monobasic ONO donor towards Co(II), Ni(II) and Cu(II) and as an ON as well as an ONO donor towards Fe(III). All the complexes have been proposed to have octahedral geometry on the basis of analytical, thermal conductivity, spectral and magnetic data. The complexes have been screened against Spodoptera litura; F (Lepidoptera: noctuiidae) for antifeeding and insect-growth-regulating activity. The results show appreciable insect-growth-regulating activity associated with metal complexation.

[Antiradical activity of 3-substituted coumarins and their effect on iron-dependent chemiluminescence].[Pubmed:1804341]

Biull Eksp Biol Med. 1991 Oct;112(10):358-60.

The antioxidant capacity of 3-Aminocoumarin, 3-oxycoumarin, 3-acetylaminocoumarin, and 3-coumarin carbonic acid has been investigated with chemiluminescence measurement and by the accumulation of TBA-active products. All coumarins were found to be antioxidants, with 3-oxy-, 3-amino- and 3-acetylamino coumarins being capable of amplifying chemiluminescence at early stages of the process.

Fluorogenic substrates for chymotrypsin with new fluorescent markers.[Pubmed:3771103]

Int J Pept Protein Res. 1986 Aug;28(2):186-91.

Several substrates for chymotrypsin Glt-Phe-NHRx have been synthesized, where RxNH2 are the compounds 3-Aminocoumarin (2), 6-aminocoumarin (3), 3-acetamido-6-aminocoumarin (4), 3-acetamido-8-aminocoumarin (5), 7-amino-4-methyl-2-quinolinone (AMQ), (6). The fluorescence properties of the new substrates and those of the corresponding free amines were examined. The compound 7-glutarylphenylalaninamido-4-methyl-2-quinolinone (Glt-Phe-AMQ), (15), provided a new suitable substrate for chymotrypsin determination. The enzymatic release of the fluorophore AMQ was measured at lambda ex = 360 nm and lambda em = 435 nm. The Km of 15 was 0.5 mM and its kcat/Km ratio was 47 M-1 s-1. By using this substrate, the detection limit of chymotrypsin was 10 ng/ml.