ABSTRACT
5-(4-Hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH) is a slowly releasing H2S donor with some neuroprotective effect.In order to study the structure-activity relationships,seventeen compounds (Y1-Y17) were synthesized by modification of ADT-OH at the aromatic ring position,and their structures were confirmed by 1H NMR,13C NMR and HR-MS.Among them,6 compounds (Y4,Y13-Y17) were novel compounds.Their effects had been evaluated on HT-22 hippocampal neuron cells damaged by glutamate with MTF method.The pharmacological results demonstrated that all the Y compounds had potent neuroprotection at most of the tested concentrations (1-100 μmol/L).Compounds Y1-Y9 and Y11 significantly improved the survival rates of the damaged cells at 1-100 μmol/L (P ＜0.01).Specially,compounds Y1,Y4,Y6-Y9,Yu are more potent than their parent compound ADT-OH at concentration of 1-10 μmol/L,which is worthy of further study.
ABSTRACT
@#H2S has a role of protecting neurons from ischemia-reperfusion injury and significantly reducing the cerebral infarction area, but high concentration of H2S can induce neurotoxicity. Memantine, a N-methyl-D-aspartic acid(NMDA)receptor antagonist, could reduce the neurotoxicity of H2S at high concentration. Nine novel structures(compounds I1-I9)were designed by coupling(4-hydroxy phenyl)-3H-1, 2-dithiole-3-thione(ADT-OH)with memantine through alkanes as linkers and synthesized by four-step reactions from ADT-OH. Their neuroprotection against damage induced by glutamate on HT-22 cells was evaluated by MTT method. The results indicated that these compounds markedly increased the survival rates of damaged HT-22 cells at the concentration of 1 μmol/L(P< 0. 01), which suggested that these compounds could preferably protect neurons against damage induced by glutamate.
ABSTRACT
<p><b>OBJECTIVE</b>To study the stability and degradation kinetics of Ketoprofen-Paeonol conjugate (Ket-Pae).</p><p><b>METHOD</b>RP-HPLC method was used to determine the solubility and partition coefficient of Ket-Pae. Stability test was carried out to investigate the factors affecting Ket-Pae. The kinetic studies of Ket-Pae degradation were conducted in different pH buffer solutions and 80% rat plasma at 37 degrees C.</p><p><b>RESULT</b>Ket-Pae showed significant degradation phenomenon at high temperature. The solubility of Ket-Pae was decreased about 200 to 300 times compared with parent drugs in water while the lnP increased about 4 times. The degradation curve displayed a V-shape, and kept maximum stability at week acidic (pH 5.0, t(1/2) = 11.4 d). Ket-Pae degraded quickly with very short half life of 1.3 min in plasma, therefore easily released ketoprofen and paeonol.</p><p><b>CONCLUSION</b>The lipophilicity of Ket-Pae is increased, its stability is affected by temperature and pH value.</p>
Subject(s)
Acetophenones , Chemistry , Drug Stability , Drugs, Chinese Herbal , Chemistry , Hydrogen-Ion Concentration , Ketoprofen , Chemistry , Kinetics , SolubilityABSTRACT
Aim: To search for new compounds with stronger anti-inflammatory activities and less gastrointestinal side effects. Methods: 2-(2, 4-Dichlorophenyl) -3-(3, 5-dimethoxyphenyl) - propenoic acid(Ⅰ) was converted to amides(Ⅱ). Their anti-inflammatory activities against xylene-induced mice ear swelling were evaluated. Results: Twelve target compounds (Ⅱ_(1-12)) were synthesized, and their structures were confirmed by IR,~1H NMR and HR-MS.Ⅱ_3 exhibited significant anti-inflammatory activity compared with CMC-Na ( P < 0. 01) and aspirin ( P < 0. 05). Conclusion: Compound Ⅱ_3 deserves further investigation.