排序方式: 共有83条查询结果,搜索用时 46 毫秒
41.
Fyaz M. D. Ismail Michael G. B. Drew Suppiah Navaratnam Roger H. Bisby 《Research on Chemical Intermediates》2009,35(4):363-377
Free radicals from one-electron oxidation of the antimalarial drug pyronaridine have been studied by pulse radiolysis. The
results show that pyronaridine is readily oxidised to an intermediate semi-iminoquine radical by inorganic and organic free
radicals, including those derived from tryptophan and acetaminophen. The pyronaridine radical is rapidly reduced by both ascorbate
and caffeic acid. The results indicate that the one-electron reduction potential of the pyronaridine radical at neutral pH
lies between those of acetaminophen (707 mV) and caffeic acid (534 mV). The pyronaridine radical decays to produce the iminoquinone,
detected by electrospray mass spectrometry, in a second-order process that density functional theory (DFT) calculations (UB3LYP/6-31+G*)
suggest is a disproportionation reaction. Important calculated dimensions of pyronaridine, its phenoxyl and aminyl radical,
as well as the iminoquinone, are presented.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
42.
Synthesis of mono-, bis-spiro- and dispiro-β-lactams and evaluation of their antimalarial activities
Aliasghar Jarrahpour Edris EbrahimiErik De Clercq Véronique SinouChristine Latour Lamia Djouhri BouktabJean Michel Brunel 《Tetrahedron》2011,67(45):8699-8704
Some new mono-, bis-spiro- and dispiro-β-lactams have been synthesized from imines derived from 9H-fluoren-9-one and a ketene derived from 9H-xanthene-9-carboxylic acid or phenoxyacetic acid by a [2+2] cycloaddition reaction in good to excellent yields varying from 45 to 83%. The biological activity of these monocyclic β-lactams was successfully investigated against Plasmodium falciparum K14 resistant strain with excellent EC50 values up to 5 μM. 相似文献
43.
Berkleasmins A-E, five new eremophilane sesquiterpenoids were isolated from the saprobic fungus Berkleasmium nigroapicale BCC 8220. The structures of the new compounds were elucidated by analyses of NMR spectroscopic and mass spectrometry data in combination with chemical means. Berkleasmins A and C exhibited cytotoxic activity against cancer cell-lines (NCI-H187, MCF-7, and KB) as well as nonmalignant Vero cells with IC50 values of 1.1-7.5 μg/mL, and these compounds also showed antimalarial activity with respective IC50 of 3.1 and 2.8 μg/mL. 相似文献
44.
Delphine Margout Sharon Wein Hermine Gandon Florence Gattacceca Henri J. Vial Françoise M. M. Bressolle 《Journal of separation science》2009,32(11):1808-1815
1,12‐Bis[5‐(2‐hydroxyethyl)‐4‐methyl‐1,3‐thiazol‐3‐ium]dodecane dibromide (SAR97276, T3) is a new antimalarial drug, which is currently being evaluated in clinical trials for severe malaria. Drug accumulation inside the parasite and a dual mechanism of action are a major strength of this compound, as it could help delay the development of resistance. The purpose of this article was to develop a rapid resolution LC‐MS method for quantifying SAR97276 in mouse tissues. The LC system consisted of Zorbax Eclipse XDB C8 (1.8 μm, 50×4.6 mm, 60°C) column. Elution with a gradient mobile phase consisting of ACN–trimethylamine‐formate buffer (pH 3) at a flow rate of 1 mL/min yielded sharp, utmost‐resolved peaks within 2 min. Tissue samples were powdered under liquid nitrogen. After protein precipitation with citric acid, SPE using WCX cartridges was used for sample preparation. There was no influence of the matrix on the detection of either SAR97276 or the IS. Assay precision was <13% and accuracy was 90–107%. The lower LOQs were 3.3 μg/kg in brain and 33 μg/kg in liver and heart. This newly developed method was used to study the tissue distribution of SAR97276 in mouse as part of the ongoing development of SAR97276. 相似文献
45.
AbstractArtemether; a sesquiterpene lactone is widely used for the treatment of malaria as artemisinin-based combination therapy (ACT). The present work involves the development and validation of sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method for quantification of artemether (ART) in polymeric nanoparticles. ART was transformed to α, β-unsaturated decalones by pre-column acid treatment to enhance the sensitivity of chromophoric group lacking ART for quantification by HPLC-UV. Waters Spherisorb® 5?µm ODS(C18) column (4.6*250?mm) with gradient elution by mobile phase comprising of ACN and PBS (10?mM; pH 6.0) was used to separate acid-treated ART. The analysis was carried at λmax of 253?nm with 20?min and 20?µL run time and injection volume, respectively. The method was found to be linear in the concentration range of 0.5–10?µg mL?1 with 0.09?µg mL?1 and 0.27?µg mL?1 as LOD and LOQ respectively. Further, the method was also found to be specific for ART in presence of blank polymeric nanoparticles, accurate (% average recovery rate 101.7?±?1.68%), precise (RSD <2%), and robust. The method was successfully used to determine % entrapment efficiency and in vitro release of ART-loaded polymeric nanoparticles with HPLC using a UV-visible detector. 相似文献
46.
Setshaba D. Khanye Scott G. Franzblau Philip J. Rosenthal Kelly Chibale 《Journal of organometallic chemistry》2011,696(21):3392-3396
Gold(III) thiosemicarbazone complexes derived from [Au(damp-C1,N)Cl2] (2), where damp = dimeth-ylaminoethylphenyl, have been synthesized. The compounds were characterised using various spectroscopic and analytical techniques, including NMR spectroscopy, mass spectrometry, infrared spectroscopy and elemental analysis. The gold complexes were screened for in vitro antimalarial and antitubercular activity. Although incorporation of the gold(III) centre into thiosemicarbazone scaffolds enhanced their efficacy against the malaria parasite Plasmodium falciparum, this trend was not observed for the antitubercular activity of selected thiosemicarbazones against the Mycobacterium tuberculosis virulent strain H37Rv. 相似文献
47.
Setshaba D. Khanye Philip J. Rosenthal Gregory S. Smith 《Journal of organometallic chemistry》2011,696(21):3296-3300
First-generation ferrocenylthiosemicarbazone metallodendrimers based on a poly(propyleneimine) dendrimer scaffold were synthesised with ferrocenylthiosemicarbazone moieties conjugated to the periphery of the branched polyamine scaffolds. The compounds were characterised by NMR and IR spectroscopy, elemental analysis and ESI-mass spectrometry. These new complexes were evaluated as bioorganometallic antimalarial agents against the Plasmodium falciparum chloroquine-resistant W2 strain. In vitro antiplasmodial assays of the dendritic ferrocenylthiosemicarbazones against the malaria parasite P. falciparum show increased efficacy compared to the precursor non-conjugated thioesters. 相似文献
48.
Pattama Pittayakhajonwut Atit Usuwan Chakapong Intaraudom Punsa Khoyaiklang Sumalee Supothina 《Tetrahedron》2009,65(31):6069-789
Investigation of the insect pathogenic fungus Torrubiella luteorostrata led to the isolation of three new macrocyclic torrubiellutins A-C (1-3) and the known pyrone diterpene 4. Structures were elucidated by spectroscopic data including 1D, 2D NMR, and MS spectral data. The absolute stereochemistry was determined by chemical means using Mosher reactions and Marfey's reagent, together with NOESY spectral data. Torrubiellutin C showed biological activities against KB, MCF-7, NCI-H187, and Vero cell lines with IC50 varying from 0.78 to 4.36 μg/mL, while compound 4 exhibited antimalaria and anti-inflammatory activity with IC50 values of 3.49 and 1.21 μg/mL, respectively. 相似文献
49.
Radhakrishnan Mahesh Sourabh Mundra Thangaraj Devadoss Lakshmi P. Kotra 《Arabian Journal of Chemistry》2019,12(7):1436-1446
The cysteine protease, falcipain-2 is an important drug target in human malaria parasite Plasmodium falciparum. A new series of 2-(4-(substituted benzoyl)-1,4-diazepan-1-yl)-N-phenylacetamide derivatives 5(a–t) were designed as per pharmacophoric requirements of falcipain-2 inhibitors using ligand-based approach. The target compounds were synthesized from the key intermediate, 2-(1,4-Diazepan-1-yl)-N-phenylacetamide, by coupling it with appropriate carboxylic acids using carbodiimide chemistry. Structural features of target compounds were characterized by spectral data (1H NMR, and mass) and elemental analyses. The purity of the final compounds was confirmed by HPLC. The compounds were tested for their in vitro falcipain-2 inhibitor activity on recombinant falcipain-2 enzyme. Five compounds 5b, 5g, 5h, 5j, 5k showed good inhibitory activity (>60%), against falcipain-2 at 10 μM concentration, and fifteen compounds showed weak to moderate inhibitor activity. Compound 5g, the most potent compound from this series showed 72% inhibition at 10 μM concentrations. 相似文献
50.
The first enantioselective synthesis of (3S,4aR,8aR)-1 (the enantiomer of natural okundoperoxide) has been accomplished. The synthesis features: 1) stereoselective installation of the peroxy functionality (16 → 17); 2) ring opening of peroxyacetal and subsequent intramolecular reaction between the hydroperoxide and the vinyl epoxide to form the peroxy six-membered ring (5 → 1). The absolute configuration of okundoperoxide was determined to be 3R,4aS,8aS by comparing specific rotations of the synthetic sample and the natural product. 相似文献