ABSTRACT
<p><b>OBJECTIVE</b>The structure-activity relationship between traditional Chinese medicine (TCM) compounds and antibacterial activity was studied by chemoinformatics approach.</p><p><b>METHOD</b>Cytoscape and its plug-in ChemViz were applied to compute the 2D chemical structure similarity and topological parameter TPSA (topological molecular polar surface area), which measures cell permeability of chemicals, between TCM compounds and clinical antibacterials. The overall degree of structure similarity was then calculated and represented by E-value for the eight categories of TCM compounds and the known antibacterials.</p><p><b>RESULT</b>Our results indicated that flavonoids showed good structural similarity with antibacterials and appropriate cell permeability, compared with those of the TCM compounds of the other categories. As flavonoids were featured by good drug safety, it suggested that they can be regarded as the preferred lead compounds skeleton structure source for further antibacterials synthesis.</p><p><b>CONCLUSION</b>The application of chemoinformatics helps explore the structure-activity relationship between TCM compounds and the antibacterial activity and search for suitable antibacterial lead compounds skeleton structure source.</p>
Subject(s)
Anti-Bacterial Agents , Chemistry , Pharmacology , Informatics , Methods , Medicine, Chinese Traditional , Software , Statistics as Topic , Structure-Activity RelationshipABSTRACT
This study is to investigate the protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism. The cardiotoxicity was induced by intraperitoneal injection of adriamycin (ADR) at a single dose of 20 mg x kg(-1). Mice were randomly divided into 5 groups (n=20): normal control group, ADR 20 mg x kg(-1) group, quercetin (50, 100, and 200 mg x kg(-1) groups, intragastric administration, once a day, for 7 days before ADR administration). The health conditions, electrocardiogram, activity of iNOS, SOD and LDH, levels of NO and MDA in serum or tissue homogenate, the ultrastructure and the expression of p53 protein in cardiac tissue of mice were observed. Compared with the normal control group, ADR decreased the amplitude of ECG's R wave (P < 0.001), increased the incidence of arrhythmia (to 60%), injured myocardial ultrastructure, increased the activity of LDH and iNOS, and levels of NO and MDA, decreased the activity of SOD, and increased the expression of p53 (P < 0.001). Compared with ADR 20 mg x kg(-1) group, the quercetin decreased the levels of LDH, iNOS, NO and MDA, increased the activity of SOD, restored the amplitude of R wave, decreased the incidence of arrhythmia and p53 expression (P < 0.001 , P < 0.01 or P < 0.05), and markedly reduced the myocardial ultrastructure injury. Quercetin had protective effect against adriamycin-induced cardiotoxicity. The mechanism may be related to its enhancing myocardial SOD activity, decreasing iNOS activity and inhibiting myocardial apoptosis.
Subject(s)
Animals , Female , Male , Mice , Apoptosis , Arrhythmias, Cardiac , Blood , Metabolism , Pathology , Doxorubicin , L-Lactate Dehydrogenase , Metabolism , Malondialdehyde , Metabolism , Myocardium , Metabolism , Myocytes, Cardiac , Metabolism , Nitric Oxide , Blood , Nitric Oxide Synthase Type II , Blood , Protective Agents , Pharmacology , Quercetin , Pharmacology , Random Allocation , Superoxide Dismutase , Metabolism , Tumor Suppressor Protein p53 , MetabolismABSTRACT
<p><b>OBJECTIVES</b>To investigate whether antisense human telomerase reverse transcriptase (hTERT) could inhibit the activity of telomerase and the proliferation of K562 cells.</p><p><b>METHODS</b>The antisense plasmid was constructed by reverse insertion of hTERT PCR product into plasmid pLNCX-neo. Then the constructed plasmid was introduced into K562 cells by liposomes-mediated DNA transfection. The inhibition effects of telomerase on the proliferation of K562 cells were analyzed by MTT and colony formation assay, the telomerase activity of K562 cells by TRAP-PCR ELISA methods.</p><p><b>RESULTS</b>The growth rate of antisense hTERT transfected K562 cells was significantly lower than those of the controls, and the colony formation capacity of the transfected cells decreased significantly (P < 0.01), the colony number is (100.33 +/- 7.57)/10(3) cells, (92.67 +/- 5.86)/10(3) cells and (50.33 +/- 6.11)/10(3) cells for control K562 cells, K562 neo cells and antisense hTERT transfected HL60 cells, respectively. The telomerase activity of antisense hTERT transfected K562 cells was significantly inhibited.</p><p><b>CONCLUSION</b>The expression of an antisense sequence to the mRNA sequence of telomerase protein subunit can inhibit the activity of telomerase, slow the cell growth and inhibit the capacity of colony formation of K562 cells.</p>