RESUMO
Pyrimidine derivatives have been the subject of much attention in pesticide and medicine fields owing to their unique biological properties. Particularly, a large number of these compounds have recently been reported to show substantial antitumor activities, and some of them have been investigated in clinical trials. Although these structurally novel compounds have a common chemical moiety of a pyrimidine ring, there are a variety of mechanisms of their antitumor action, such as, inhibition of cyclin-dependent-kinases, inhibition of protein tyrosine kinase, inhibition of carbonic anhydrases, inhibition of dihydrofolate reductase and disruption of microtubule assembly. In this paper, we described the latest advances in the research of such pyrimidine derivatives as antitumor drug according to their action on targets.
Assuntos
Animais , Humanos , Antineoplásicos , Química , Farmacologia , Usos Terapêuticos , Inibidores da Anidrase Carbônica , Farmacologia , Proliferação de Células , Quinases Ciclina-Dependentes , Antagonistas do Ácido Fólico , Farmacologia , Neoplasias , Tratamento Farmacológico , Patologia , Proteínas Tirosina Quinases , Pirimidinas , Química , Farmacologia , Usos Terapêuticos , Tetra-Hidrofolato Desidrogenase , Farmacologia , Moduladores de Tubulina , Farmacologia , Usos TerapêuticosRESUMO
<p><b>OBJECTIVE</b>To synthesize cyclin-dependent kinase (CDKs) inhibitors and assay their antitumor activities.</p><p><b>METHODS</b>A series of pyrimidines containing different arylamino and 1-(methylsulfonyl)piperidin moieties were designed by combining the segments 1-(methylsulfonyl)piperidin and pyrimidine heterocycles according to the super-position principle of the reinforcement of biological activities.</p><p><b>RESULTS</b>Their structures were characterized by MS and 1H NMR spectra and all the synthesized compounds were screened for their antimicrobial activity with MTT assay.</p><p><b>CONCLUSION</b>The preliminary bioassay showed that compound 3 b displayed good antitumor activity (IC(50)=13.6 µmol/L). The preliminary structure activity relationship analysis of these analogues suggest that the steric factor may have important impact on the anti-tumor activity.</p>
Assuntos
Humanos , Antineoplásicos , Química , Farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Pirimidinas , Química , Farmacologia , Relação Estrutura-AtividadeRESUMO
<p><b>OBJECTIVE</b>To establish a HPLC-based method for simultaneous determination of 2 classes of compounds (flavonoids and chromones) and 6 their effective components,(including prin-O-glucosylcimifugin, cimifugin, 4'-O-beta-D-glucosyl- 5-O-methylvisamminol, quercetin, sec-o-glucosylhamaudol and formononetin), in Yupingfeng Decoction.</p><p><b>METHODS</b>HPLC-based separation of the agents was performed on Agilent Extend-C(18) column (4.6 mm x 250 mm, 5 microm) at 25 degrees with the mobile phase of MeOH-1% acetic acid water solution (gradient elution), flow rate of 0.8 ml/min and detection wavelength of 254 nm.</p><p><b>RESULTS AND CONCLUSION</b>HPLC allowed simultaneous quantitative determination of the 6 components in Yupingfeng Decoction, and they showed good linear relationships when their sample amount ranged 90-1810 ng, 97-1940 ng, 190-1906 ng, 105-3144 ng, 88-2625 ng and 109-3279 ng, respectively, with correlation coefficients all beyond 0.9999 and average recovery rates of 98.2%, 99.1%, 97.3%, 97.8%, 98.8% and 99.2%, respectively. This simple and convenient method accommodated a broad linear range with high sensitivity and precise and reproducible results.</p>