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.

44 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    African journal of pharmacy and pharmacology 12/2014; 8(48):1213-1227. DOI:10.5897/AJPP2014.4153 · 0.84 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    PLoS ONE 07/2013; 8(7):e67945. DOI:10.1371/journal.pone.0067945 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A novel series of 6-bromo-3-(2-morpholino methyl amino)-6-substituted phenyl pyrimidine-4-yl-2H-chromone-2-one (6aM–6jM) and 3-(2-((piperidine-1-yl)methyl amino)-6- substituted phenylpyrimidin-4-yl)-6-bromo-2H-chromone-2-one (6aP–6jP) have been synthesized from 3-(2-amino-6-pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (5a–5j) which were synthesized from 3-acetyl-6-bromo-2H-chromen-2-one (3). The reactions were carried out by conventional and microwave method. The salient feature of microwave method are rapid reaction rate, cleaner reaction condition, and enhancement in chemical yield compared to conventional method, the structures of the synthesized compounds were characterized by I.R., 1H NMR, 13C NMR, Mass spectroscopic techniques. All the compounds screened at a dose of 20 mg/kg body weight by in vivo analgesic activity. Among all the synthesized compounds, compound 6aP, 6aM, 6cM, 6iM, and 6jM showed significant analgesic activity and compounds 6cM and 6iM showed highly significant activity against the standard drug Diclofenac sodium using acetic acid-induced writhing model. Among all the synthesized compounds which show potent analgesic activity such as 6aP, 6aM, 6cM, 6iM, and 6jM were further evaluated for acute- ulcerogenic activity. Among all compound 6cM and 6iM was found to be most promising analgesic agent devoid of ulcerogenic effects.
    Medicinal Chemistry Research 11/2011; 21(11). DOI:10.1007/s00044-011-9907-7 · 1.40 Impact Factor
Show more


44 Reads

Rangappa Keri