ABSTRACT
<p><b>AIM</b>To determine the effects of azide methyl anthraquinone derivative (AMAD) on growth inhibition and inducing apoptosis of multidrug resistant (MDR) KBv200 cells and parental drug-sensitive KB cells.</p><p><b>METHODS</b>Cytotoxicity was determined by tetrazolium (MTF) assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (deltapsi(m)) in cells were labeled with DCFH-DA and DiOC6 and tested by flow cytometry. Annexin V stain and DNA ladder were used to examine the apoptosis of KB and KBv200 cells induced by AMAD.</p><p><b>RESULTS</b>AMAD was shown to inhibit the growth of KB and KBv200 cells significantly in a concentration-dependent manner, with mean IC50 of 0.36 and 0.45 micromol x L(-1), respectively. The generation of ROS increased obviously after the cells were treated with AMAD for 12 h, up to the peak in 24 h, meanwhile the levels of deltapsi(m) were time-dependently decreased. DNA fragmentation appeared on the agarose gel. Annexin V stain showed AMAD induced apoptosis of KB and KBv200 cells also in a concentration-dependent manner.</p><p><b>CONCLUSION</b>AMAD showed inhibitory effect on both MDR KBv200 cells and parental drug-sensitive KB cells. The mechanism of action was associated with the increase of the cellular ROS level and the decrease of the mitochondrial membrane potential induced by AMAD, which result in cell apoptosis.</p>
Subject(s)
Humans , Anthraquinones , Chemistry , Pharmacology , Antineoplastic Agents , Chemistry , Pharmacology , Apoptosis , Cell Proliferation , Dose-Response Relationship, Drug , Drug Resistance, Multiple , Drug Resistance, Neoplasm , KB Cells , Mitochondria , Physiology , Molecular Structure , Mouth Floor , Mouth Neoplasms , Pathology , Reactive Oxygen Species , Metabolism , Vincristine , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To prepare cryptotanshinone (CT)-cyclodextrin inclusion compound and improve dissolution of CT.</p><p><b>METHOD</b>Inclusion ratio was determined by plotting the phase solubility curve of CT versus hydroxypropyl-beta-cyclodextrin (HPCD). CT-cyclodextrin inclusion compound was made by wet grinding method. Properties of the inclusion compound was investigated by in vitro dissolution test, DTA and IR spectrum.</p><p><b>RESULT</b>Inclusion ratio of CT versus HPCD was 1:1. Dissolution of CT-HPCD inclusion compound at 45 min was 21.6 times of material drug.</p><p><b>CONCLUSION</b>Dissolution of CT was improved remarkably in CT-HPCD inclusion compound. The complexation force of the inclusion compound was hydrogen bond formed by carbonyl group of CT and hydroxyl group of HPCD.</p>
Subject(s)
2-Hydroxypropyl-beta-cyclodextrin , Biological Availability , Drug Carriers , Drugs, Chinese Herbal , Chemistry , Phenanthrenes , Chemistry , Salvia miltiorrhiza , Chemistry , Solubility , Technology, Pharmaceutical , Methods , Time Factors , beta-Cyclodextrins , ChemistryABSTRACT
<p><b>AIM</b>To study the synthesis and antitumour activities of some aryl-substituted pteridines.</p><p><b>METHODS</b>A series of aryl-substituted pteridines were synthesized from 4, 6-diamino-5-nitrosopyrimidines by cyclization with 4-aminophenylacetonitriles. The antitumour activities were tested by MTT method.</p><p><b>RESULTS</b>Nine new compounds (I-III) were synthesized and their structures were characterized by EA, IR, 1HNMR and MS spectra. Compounds I-III showed antitumour activities in vitro.</p><p><b>CONCLUSION</b>Compounds I-III showed remarkable antitumour activities in vitro. No interaction was determined between the title compounds and calf thymus DNA. It indicated that these compounds possibly inhibit dihydrofolate reductase (DHFR) or other enzymes on which folic acid depends.</p>