ABSTRACT
In this work, the chemical cross-linked interaction between chitosan polymeric chains and synthetic terephthaloyl diisothiocyanate as a cross-linker was accomplished in order to fabricate three dimensional cross-linked chitosan hydrogel. This cross-linked hydrogel with considerable characteristics including high stability and homogeneity in aqueous solution (water) and high porosity was applied as new substrate for generation of new magnetic terephthaloyl thiourea cross-linked chitosan nanocomposite. The features of this new magnetic nanocomposite were characterized by FT-IR, EDX, FE-SEM, TEM and VSM analysis. The Size distribution of nanoparticles according to the size histogram of FE-SEM images was estimated between 30 and 40â¯nm. The performance of designed magnetic nanocomposite was evaluated by magnetic fluid hyperthermia procedure. Under the alternating magnetic field (AMF), the specific absorption rate (66.92â¯w·g-1) was determined and as well, its saturation magnetization value was reported 78.43â¯emu·g-1.
Subject(s)
Chitosan/chemistry , Hydrogels/chemistry , Magnetite Nanoparticles/chemistry , Neoplasms/therapy , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Chitosan/chemical synthesis , Chitosan/pharmacology , Humans , Hydrogels/chemical synthesis , Hydrogels/pharmacology , Hyperthermia, Induced/methods , Nanocomposites/chemistry , Phthalic Acids/chemical synthesis , Phthalic Acids/chemistry , Spectroscopy, Fourier Transform Infrared , Thiourea/chemical synthesis , Thiourea/chemistryABSTRACT
In the present study, a series of 13-ß-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells (HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase (SOD), malonyldialdehyde (MDA), nitric oxide (NO), and lactic dehydrogenase (LDH), which were superior to that of the positive control vitamin E. Further more, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.
Subject(s)
Antioxidants/pharmacology , Drugs, Chinese Herbal/pharmacology , Endothelium, Vascular/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Oxidative Stress/drug effects , Phthalic Acids/pharmacology , Sesquiterpenes/pharmacology , Succinates/pharmacology , Antioxidants/chemical synthesis , Antioxidants/metabolism , Cells, Cultured , Curcuma/chemistry , Drug Stability , Drugs, Chinese Herbal/chemistry , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Humans , Hydrogen Peroxide/metabolism , Malondialdehyde/metabolism , Nitric Oxide/metabolism , Oxidation-Reduction , Phthalic Acids/chemical synthesis , Sesquiterpenes/chemical synthesis , Succinates/chemical synthesis , Superoxide Dismutase/metabolismABSTRACT
At the end of the last century tariquidar (XR9576) was synthesized, pharmacologically investigated, and classified as a promising 3rd generation P-glycoprotein (P-gp) modulator. Following the discovery of BCRP in 1998 an increasing number of substances were studied in relation to their potency to interact with this transporter. Recently it has been shown that XR9576 inhibits both P-gp and BCRP transport function similarly to GF120918 (elacridar). This observation prompted us to investigate 5 XR compounds and 25 structurally related derivatives synthesized in our laboratory for their BCRP inhibitory effect. The biological activity data were determined by our new Hoechst 33342 assay that has been transferred from P-gp to BCRP overexpressing cells. 3D-QSAR models (CoMFA and CoMSIA) were generated and validated by the leave-many-out method and the scrambling stability test. The best models yielded an internal predictive squared correlation coefficient higher than 0.8 and contained steric, electrostatic, hydrophobic, and hydrogen bond donor fields. To our knowledge, this is the first 3D-QSAR analysis of BCRP inhibitors. Additionally the biological activity data determined in P-gp overexpressing cells on one side and BCRP overexpressing cells on the other side were compared to identify selective and non-selective inhibitors of P-gp and BCRP. The results may help to get a better insight which structural elements are necessary to direct the interaction of these compounds with P-gp and/or BCRP.
Subject(s)
ATP-Binding Cassette Transporters/antagonists & inhibitors , Breast Neoplasms/drug therapy , Neoplasm Proteins/antagonists & inhibitors , Phthalic Acids/pharmacology , Quantitative Structure-Activity Relationship , Quinolines/pharmacology , ATP Binding Cassette Transporter, Subfamily B/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily G, Member 2 , Crystallography, X-Ray , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Female , Humans , Models, Molecular , Molecular Structure , Phthalic Acids/chemical synthesis , Phthalic Acids/chemistry , Quinolines/chemical synthesis , Quinolines/chemistry , Reproducibility of Results , Stereoisomerism , Time Factors , Tumor Cells, CulturedABSTRACT
The novel fibrinogen receptor antagonists containing fragments of 7-amino-1,2,3,4-tetrahydroisoquinoline and isophthalic acids were synthesized and successfully tested for their ability to inhibit platelet aggregation in vitro and to block FITC-Fg binding to alpha(IIb)beta(3) on washed human platelets.