Publications (42) View all
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Article: Synthesis and antibacterial evaluation of rhodanine-based 5-aryloxy pyrazoles against selected methicillin resistant and quinolone- resistant Staphylococcus aureus (MRSA and QRSA)
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ABSTRACT: a b s t r a c t With an intention to synergize the anti-bacterial activity of 5-aryloxy pyrazole and rhodanine deriva-tives, eight series of hybrid compounds have been synthesized and evaluated for their antibacterial activity. The majority of the synthesized compounds showed good inhibitory activity against selected methicillin resistant and quinolone-resistant Staphylococcus aureus (MRSA, QRSA) with minimum inhibitory concentration (MIC) values in the range of 1e32 mg/mL. The cytotoxicity test suggests that these compounds exhibited in vitro antibacterial activity at non-cytotoxic concentrations. These studies therefore suggest that rhodanine-based 5-aryloxy pyrazoles are interesting scaffolds for the develop-ment of novel Gram-positive antibacterial agents. Ó 2012 Elsevier Masson SAS. All rights reserved.European Journal of Medicinal Chemistry 01/2013; 60:376. · 3.35 Impact Factor -
Article: Synthesis and Biological Evaluation of Furan-chalcone Derivatives as Protein Tyrosine Phosphatase Inhibitors
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ABSTRACT: Protein tyrosine phosphatase1B (PTP1B) has become an attractive therapeutic target for the treatment of type 2 diabetes mellitus and obesity due to its negative regulator in the insulin and leptin receptor pathways. 1,2 In recent years, following the elucidation of the protein structure of PTP1B, many synthetic PTP1B inhibitors with submicromolar or nanomolar activities have been discovered through high-throughput screening and structure-based design. However, the low selectivity and poor pharmacokinetic properties of these synthetic inhibitors mean that novel PTP1B inhibitors with improved pharmacological properties are still sought after. 3,4 Recently, several chalcones derived from natural products and their derivatives have been identified as PTP1B inhibitors. 5-7 These reports suggested that chalcones might be promising PTP1B inhibitors. To develop a new type of PTP1B inhibitors based on the chalcone structure, we decided to further extend our research using the new chaclone core, which possesses a heterocycle. In the present study, we performed the in vitro screening of some heterocyclic chalcone derivatives bearing thiofuran, furan, pyridine and quinoline moieties from our in-house collection, and identified (E)-3-(furan-2-yl)-1-phenylprop-2-en-1-one (1b) to be a moderate PTP1B inhibitor, with an IC 50 value of 6.94 ± 0.69 µM (Fig. 1). To obtain more potent PTP1B inhibitors and further investigate the structure-activity relationships, we tried to design and synthesize a series of furan-chalcone derivatives with variation of substituents using 1b as the lead compound. The synthetic pathways 1a-e and 2a-m are illustrated in Scheme 1. The synthesis procedure and spectral data of the compounds 1a-e, 2a-m were previously described by our laboratory. 8 The inhibitory activities of all the synthesized compounds against PTP1B were measured using p-nitrophenyl phos-phate (pNPP) as a substrate, and the results are summarized in Table 1. The known PTP1B inhibitor, ursolic acid (3.40 ± 0.17 µM), was used as the positive control. 6 As shown in Table 1, 11 compounds out of the 14 test compounds dose-dependently inhibited PTP1B with IC 50 values ranging from 2.49 ± 0.23 to 35.31 ± 4.50 µM. The IC 50 values of compounds 2b and 2m (2.90 ± 0.12, 2.49 ± 0.23 µM, respectively) were better or similar to that of ursolic acid. Comparing with compound 1b, compounds 2b and 2m had potent PTP1B inhibitory effects. It seemed that the substituent on chalcone A ring might be important in the inhibitory activity of PTP1B. However, compounds 2a and 2c-l that bore substituent(s) on the A ring show less activity than 1b. These results indicated that the character of sub-stituent on the A ring had a signicant inuence on the PTP1B inhibitory activity. Except 2a and 2i, compounds with elec-tron-withdrawing groups (i.e., 2b-f) seemed to show better a These authors contributed equally to this work.Bulletin- Korean Chemical Society 01/2013; 34(4):1023. · 0.91 Impact Factor -
Article: Synthesis and Biological Evaluation of [1,2,4]Triazolo [3,4-a]phthalazine and Tetrazolo[5,1-a]phthalazine Derivatives Bearing Substituted Benzylpiperazine Moieties as Positive Inotropic Agents
Chemical Biology & Drug Design 01/2013; 81:591. · 2.28 Impact Factor -
Article: Synthesis and biological evaluation of 5-aryloxypyrazole derivatives bearing a rhodanine-3-aromatic acid as potential antimicrobial agents.
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ABSTRACT: Three novel series of 5-aryloxypyrazole derivatives have been synthesized and tested for their antibacterial activity. The majority of the synthesized compounds showed potent inhibitory activity against Gram-positive bacteria Staphylococcus aureus 4220, especially against the strains of multidrug-resistant clinical isolates (MRSA3167/3506 and QRSA3505/3519). Among which compounds IIIb, IIIg and IIIm showed the most potent levels of activity (MIC=1μg/mL) against the multidrug-resistant strains. And cytotoxic activity assay showed that the compounds tested did not affect cell viability on the Human cervical (HeLa) cells at their MICs. The current study therefore suggests that 5-aryloxypyrazoles bearing a rhodanine-3-aromatic acid moiety are promising scaffolds for the development of novel Gram-positive antibacterial agents.Bioorganic & medicinal chemistry letters 10/2012; · 2.65 Impact Factor -
Article: Synthesis and Positive Inotropic Evaluation of (E)-2-(4-Cinnamylpiperazin-1-yl)-N-(1-substituted-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides.
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ABSTRACT: A series of (E)-2-(4-cinnamylpiperazin-1-yl)-N-(1-substituted-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides were synthesized and evaluated for their positive inotropic activity by measuring the left atrium stroke volume on isolated rabbit heart preparations. This class of compounds presented favorable in vitro activity compared with the standard drug, milrinone, among which N-(1-(3-chlorophenyl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(4-cinnamylpiperazin-1-yl)acetamide 5e was found to be the most potent with 16.58 ± 0.11% increased stroke volume (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10(-5) M. The chronotropic effects of the compounds having inotropic effects were also evaluated.Archiv der Pharmazie 09/2012; · 1.71 Impact Factor
