ABSTRACT
Multidrug resistance in cancer is a major cause of failure in cancer chemotherapy. In search of new compounds with strong reversal activity and simple molecular structure, we have synthesized a series of compounds in which different substituents were linked to the 2-position of the 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)- tetrahydroisoquinoline system. Compounds were analyzed for their cytotoxicity by MTT in K562 cell line in vitro, all of the derivatives exhibited little cytotoxic activity. In the meantime, these compounds were evaluated by MTT in K562/A02 cell line in vitro, 6e, 6h and 7c exhibited similar or more potent activities than verapamil with the IC50 values at 0.66, 0.65 and 0.96µM, and with the ratio factor of 24.13, 24.50 and 16.59, respectively.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Drug Design , Tetrahydroisoquinolines/chemical synthesis , Tetrahydroisoquinolines/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , Inhibitory Concentration 50 , K562 Cells , Molecular Structure , Tetrahydroisoquinolines/chemistryABSTRACT
In the title compound, C(9)H(6)FNO(2), the carboxyl group is twisted slightly away from the indole-ring plane [dihedral angle = 7.39â (10)°]. In the crystal, carboxyl inversion dimers linked by pairs of O-Hâ¯O hydrogen bonds generate R(2) (2)(8) loops and N-Hâ¯O hydrogen bonds connect the dimers into (10[Formula: see text]) sheets.
ABSTRACT
Multidrug resistance in tumor cells poses a major obstacle to efficient chemotherapy. Several types of agents have been recognized as multidrug resistance inhibitors, among which the tetrahydroisoquinolines is the most studied. In current study 16 furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline were synthesized. Their cytotoxic activities and effects in reversing multidrug resistance have been evaluated. The results revealed that these compounds had moderate cytotoxic effects. Compounds 7a-f, 7h, and 7l showed higher cytotoxicities than the rest, but lower than adriamycin on K562 cell line. Compounds 7d, 7f, and 7l exhibited potent MDR reversal activities on K562/A02 cell line. The accumulation assay indicated that compounds 7d, 7f, and 7l significantly increased the intracellular accumulation of rhodamine123 in K562/A02 cells. Furthermore, these three compounds produced high concentrations of NO in K562/A02 cells. Potentially, the high concentrations of NO produced by NO donor moieties will lead to an increased cytotoxicity to K562/A02 cells. Our results suggested that compounds 7d, 7f, and 7l had anticancer effects, as well as multidrug resistance reversal effects.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Doxorubicin/pharmacology , Drug Resistance, Neoplasm , Tetrahydroisoquinolines/chemical synthesis , Tetrahydroisoquinolines/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Combined Chemotherapy Protocols , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival , Doxorubicin/metabolism , Drug Design , Drug Evaluation, Preclinical , Drug Resistance, Multiple , Drug Screening Assays, Antitumor , Drug Synergism , Humans , Inhibitory Concentration 50 , K562 Cells , Molecular Targeted Therapy , Nitric Oxide/metabolism , Rhodamine 123/metabolism , Tetrahydroisoquinolines/chemistry , Tetrahydroisoquinolines/metabolism , Triazoles/chemistry , Triazoles/metabolism , Verapamil/metabolism , Verapamil/pharmacologyABSTRACT
Phytochemical investigation of the ethanol extract of Pedicularis kansuensis Maxim. led to the isolation of one new triterpenoid and two new phenylpropanoid glycosides, along with ten known compounds. Their structures were established by extensive 1D and 2D NMR, as well as other spectrum analysis. Biological evaluation of the three new compounds against Hela cell and Hep-6 cell with MIC values ranging from 9 to 20 µg/ml.
Subject(s)
Antineoplastic Agents/pharmacology , Glycosides/pharmacology , Pedicularis/chemistry , Triterpenes/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Glycosides/chemistry , Glycosides/isolation & purification , Humans , Microbial Sensitivity Tests , Plant Components, Aerial/chemistry , Plant Extracts/chemistry , Triterpenes/chemistry , Triterpenes/isolation & purificationABSTRACT
The racemic title compound, C(14)H(12)ClNO, contains two mol-ecules in the asymmetric unit. The dihedral angles between the phenyl and benzene rings are 84.03â (15) and 83.92â (13)°. The crystal structure involves inter-molecular N-Hâ¯O, C-Hâ¯Cl and C-Hâ¯O hydrogen bonds, linking mol-ecules into layers parallel to the (100) plane.
ABSTRACT
The problem that the present sediment theory does not consider sludge recirculation effect on the efficiency of particle settling is studied. Based on the longitudinal mixing settling theory, an imperfect sediment model that takes reflux ratio in consideration is built. According to the established model, the study analyzes the effect of sludge recirculation taken by suction dredge on particle setting, in horizontal sedimentation tank. Specifically, the relation between overplus of sewerage suspension and sedimentation rate was chosen as an example. Shown as a result, when sludge recirculation is not taken in consideration, efficiency of particle settling is 72.8%. However, when sludge recirculation increases from 0.5 to 3.0, efficiency of particle settling decreases from 71.1% to 50.9%, which is smaller than efficiency of particle settling without recirculation; and when sludge recirculation is 3.0, efficiency of particle settling is 50.9%, which is approximately 30% less than efficiency of particle settling without recirculation. So, sludge recirculation make efficiency of particle settling is smaller than efficiency of particle settling without recirculation, and the efficiency of particle settling reduces with the increase of reflux ratio.
Subject(s)
Geologic Sediments/chemistry , Models, Theoretical , Sewage/chemistry , Water Purification/instrumentation , Chemical Precipitation , Particle Size , Water Purification/methodsABSTRACT
Considering the difficulty of fuzzy synthetic evaluation method in calculation of the multiple factors and ignorance of the relationship among evaluating objects, a new weight evaluation process using entropy method was introduced. This improved method for determination of weight of the evaluating indicators was applied in water quality assessment of the Three Gorges reservoir area. The results showed that this method was favorable for fuzzy synthetic evaluation when there were more than one evaluating objects. One calculation was enough for calculating every monitoring point. Compared with the original evaluation method, the method predigested the fuzzy synthetic evaluation process greatly and the evaluation results are more reasonable.
