ChemInform Abstract: Analgesic, anti-Pyretic and DNA Cleavage Studies of Novel Pyrimidine Derivatives of Coumarin Moiety.

P.G. Department of Studies in Chemistry, Karnatak University, Pavate Nagar, Dharwad 580 003, Karnataka, India.
European Journal of Medicinal Chemistry (Impact Factor: 3.45). 03/2010; 45(6):2597-605. DOI: 10.1016/j.ejmech.2010.02.048
Source: PubMed


A novel series of 4-[4-(6-phenyl-pyrimidin-4-yl)-phenoxymethyl]-chromen-2-ones [5-7(a-e)] were synthesized from various 4-bromomethyl coumarins 1(a-e). The synthesized compounds were screened for in-vivo analgesic and anti-pyretic activities at a dose of 25 and 100 mg/kg body weight (b.w), respectively. Among them, compounds 5(d), 6(c) and 7(d) exhibited significant analgesic activity comparable with standard drug analgin using Tail-flick model. Compounds 5(a) and 7(a-d) showed significant anti-pyretic activities comparable with standard drug aspirin using yeast-induced pyrexia model. DNA cleavage study by agarose gel electrophoresis method was also studied. Qualitative SAR studies indicate that, compounds with amino group at 2-position of pyrimidine ring enhances analgesic and anti-pyretic activities and compounds with hydroxyl and thio group at 2-position of pyrimidine ring increase DNA cleavage activities.

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Available from: Kallappa M. Hosamani, Jan 08, 2016
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    • "Coumarin and its derivatives, a class of quite important lactones compounds containing a structure of benzene ring and a-pyrone, occupy an important position in medicinal chemistry, which have latent ability to exert noncovalent interactions (p-p, hydrophobic, electrostatic interactions, hydrogen bonds, metal coordination and van der Waals force etc.) with the various active sites in organisms [15]. As medicines, many of them display a wide range of bioactivities such as antibacterial, antifungal [16], anticoagulant [17], antioxidant [18], anti-inflammatory [19], analgesic [20], anticancer [21], anti-HIV [22] and antiviral [23] efficacies. For instance, the 7- substituted coumarin (I) showed a stronger efficacy against Fusarium oxysporum with MIC value of 19 mg/mL [24]; the 4-chloro-3- thiadiazole-imino coumarin (II) exhibited significant activity against Candida albicans with inhibitory zone diameter of 15 mm in 10 mg/mL [25]; and the 4-azidomethyl coumarin sulfonamides derivatives (III) showed excellent antifungal efficacies against C. albicans and F. oxysporum with MIC values of 1 mg/mL, which were 8 times more potent than fluconazole (MIC ¼ 8 mg/mL) [26]. "
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    ABSTRACT: A series of novel phosphoramidate derivatives of coumarin have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their chitin synthase inhibition activity and antimicrobial activity in vitro. The bioactive assay manifested that most of the target compounds exhibited good efficacy against CHS and a variety of clinically important fungal pathogens. In particular, compound 7t with IC50 of 0.08 mM against CHS displayed stronger efficiency than the reference Polyoxin B with IC50 of 0.16 mM. In addition, the apparent Ki values of compound 7t was 0.096 mM while the Km of Chitin synthase prepared from Candida tropicalis was 3.86 mM for UDP-Nacetylglucosamine, and the result of the Ki showed that the compounds was a non-competitive inhibitor of the CHS. As far as the antifungal activity is concerned, compounds 7o, 7r and 7t were highly active against Aspergillus flavus with MIC values in the range of 1 μg/mL to 2 μg/Ml while the results of antibacterial screening showed that these compounds have negligible actions to the tested bacteria. These results indicated that the design of these compounds as antifungal agents was rational.
    Full-text · Article · Nov 2015 · European Journal of Medicinal Chemistry
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    • "E-mail: Author(s) agree that this article remain permanently open access under the terms of the Creative Commons Attribution License 4.0 International License distributed in nature and since many of coumarin derivatives have been found useful applications as therapeutic agents with broad and diverse biological activities, including anti-inflammatory (Stefani et al., 2012; Lin et al., 2006), analgesic and antipyretic (Keri et al., 2010) activities. "
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    ABSTRACT: Starting from the 8-acetyl-4-methyl-6-nitro-2-oxo-2H-chromen-7-yl benzoate I, 8-(3-arylacryloyl)-4-methyl-6-nitro-2-oxo-2H-chromen-7-yl benzoates (chalcones) II were synthesized and further used for the synthesis of two new series of 8-(2-imino/oxo/thioxo pyrimidin-4-yl)-4-methyl-6-nitro-2-oxo-2H-chromen-7-yl benzoates III-V and 8-(pyrazol-3-yl)-4-methyl-6-nitro-2-oxo-2H-chromen-7-yl benzoates VI and VII. All of the synthesized compounds were assessed for their anti-inflammatory activity using the carrageenan-induced hind paw edema method. The 8-acetyl coumarin I exhibited the most potent activity with 24.12% inhibition 2 h post carrageenan injection and 16.38% inhibition 3 h post carrageenan injection. In addition, an in silico comparative COX1 and COX2 docking study was performed in order to explain the possible interactions and the docking scores of all the compounds into the crystal structure of cyclooxygenases (Cox1 and Cox2) enzymes using Autodock 4.2 program. The results revealed more selective COX2 binding affinities of all the compounds over Cox1, whereas, only compound IVc exhibited non-selective COX1 and COX2 fitting.
    Full-text · Article · Dec 2014 · African journal of pharmacy and pharmacology
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    • "Compounds 2 to 6 were synthesized from different substituted phenols treated with ethyl-4-bromoacetoacetate. The ethyl-4-bromoacetoacetate was obtained by bromination of ethylacetoacetate [39]. Ethyl-4-bromoacetoacetate was then treated with 4-methoxy phenol, 3-cresol, 4-cresol, 1-napthol and 2-napthol under Pechmann cyclisation condition using concentrated sulphuric acid to afford the differentially substituted 4-bromomethyl coumarins (2–6), respectively [40,41]. All coumarins were dissolved in pure DMSO to give a 20 mM solution. "
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    ABSTRACT: Selective alkylation of RNA nucleotides is an important field of RNA biochemistry, e.g. in applications of fluorescent labeling or in structural probing experiments, yet detailed structure-function studies of labeling agents are rare. Here, bromomethylcoumarins as reactive compounds for fluorescent labeling of RNA are developed as an attractive scaffold on which electronic properties can be modulated by varying the substituents. Six different 4-bromomethyl-coumarins of various substitution patterns were tested for nucleotide specificity of RNA alkylation using tRNA from Escherichia coli as substrate. Using semi-quantitative LC-MS/MS analysis, reactions at mildly acidic and slightly alkaline pH were compared. For all tested compounds, coumarin conjugates with 4-thiouridine, pseudouridine, guanosine, and uridine were identified, with the latter largely dominating. This data set shows that selectivity of ribonucleotide alkylation depends on the substitution pattern of the reactive dye, and even more strongly on the modulation of the reaction conditions. The latter should be therefore carefully optimized when striving to achieve selectivity. Interestingly, the highest selectivity for labeling of a modified nucleoside, namely of 4-thiouridine, was achieved with a compound whose selectivity was somewhat less dependent on reaction conditions than the other compounds. In summary, bromomethylcoumarin derivatives are a highly interesting class of compounds, since their selectivity for 4-thiouridine can be efficiently tuned by variation of substitution pattern and reaction conditions.
    Full-text · Article · Jul 2013 · PLoS ONE
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