ABSTRACT
Objective: To explore the structure and reaction sites of the reaction products of chlorogenic acid and sodium sulfite,and the chemical changes of chlorogenic acid in Lonicerae Japonicae Flos after sulfur fumigating. Method: Chlorogenic acid was reacted with sodium sulfite under mild conditions. Liquid chromatography-mass spectrometry-ion trap-time-of-flight (LC-MS-IT-TOF) and 1H nuclear magnetic resonance spectroscopy (1H-NMR) detection techniques were used to detect the reaction products,and the sulfur-fumigated and unsulfurized Lonicerae Japonicae Flos water extract was detected by LC-MS-IT-TOF. Result: After analyzing the mass spectrometry data of fragment ion,molecular cleavage and accurate molecular weight,according to the results of nuclear magnetic signals of chemical shift,peak intensity and peak splitting, the products of chlorogenic acid and sodium sulfite were preliminarily identified as chlorogenic acid α,β-unsaturated carbonyl addition product:3-((3-(3,4-dihydroxyphenyl)-2-sulfopropyl)oxy)-1,4,5-trihydroxycyclohexane-1-carboxylic acid or 3-((3-(3,4-dihy droxyphenyl)-3-sulfopropyl)oxy)-1,4,5-trihydroxycyclohexane-1-carboxylic acid,and the same characteristic fragments were detected as the addition product in the sulfur fumigated Lonicerae Japonicae Flos,but not found in the unsulfurized. Conclusion: It is the first time to demonstrate the structure and reaction sites of chlorogenic acid and sulfurous acid reaction products,and detect the chlorogenic acid sulfite addition product in sulfur-fumigated Lonicerae Japonicae Flos. Although it is still unclear how the sulfite addition compound produced by sulphur Lonicerae Japonicae Flos affects the efficacy and toxicological activity of Lonicerae Japonicae Flos,we shall still pay attention to the changes of active ingredients in sulphuric medicinal materials. Besides,this study can also provide reference for the studies of chemical composition changes after sulfuration of traditional Chinese medicine containing α,β-unsaturated carbonyl structure.
ABSTRACT
Novel series of limonin derivatives (V-A-1-V-A-8, V-B-1-V-B-8) were synthesized by adding various tertiary amines onto the C (7)-position of limonin. The synthesized compounds possessed favorable physicochemical property, and the intrinsic solubility of the novel compounds were significantly improved, compared with limonin. Different pharmacological models were used to evaluate the analgesic and anti-inflammatory activities of the target compounds. Compound V-A-8 exhibited the strongest in vivo activity among the novel limonin analogs; its analgesic activity was more potent than aspirin and its anti-inflammatory activity was stronger than naproxen under our testing conditions.
Subject(s)
Animals , Humans , Mice , Analgesics , Chemistry , Anti-Inflammatory Agents , Chemistry , Drug Discovery , Edema , Drug Therapy , Limonins , Chemistry , Molecular Structure , Pain , Drug TherapyABSTRACT
Novel series of limonin derivatives (V-A-1-V-A-8, V-B-1-V-B-8) were synthesized by adding various tertiary amines onto the C (7)-position of limonin. The synthesized compounds possessed favorable physicochemical property, and the intrinsic solubility of the novel compounds were significantly improved, compared with limonin. Different pharmacological models were used to evaluate the analgesic and anti-inflammatory activities of the target compounds. Compound V-A-8 exhibited the strongest in vivo activity among the novel limonin analogs; its analgesic activity was more potent than aspirin and its anti-inflammatory activity was stronger than naproxen under our testing conditions.
Subject(s)
Animals , Humans , Mice , Analgesics , Chemistry , Anti-Inflammatory Agents , Chemistry , Drug Discovery , Edema , Drug Therapy , Limonins , Chemistry , Molecular Structure , Pain , Drug TherapyABSTRACT
In order to search for novel inhibitors of Na+/H+ exchanger isoform-1 (NHE-1), nine feruloylagmatine analogues were designed and synthesized from ferulic acid and agmatine. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR and mass spectra, among which compounds 5f-5i were novel compounds. The results of preliminary pharmacological test showed that some of the compounds possessed strong NHE-1 inhibitory activity, among which compounds 5a, 5b and 6c were more potent than cariporide in NHE-1 inhibition.
Subject(s)
Animals , Female , Male , Rats , Agmatine , Chemistry , Pharmacology , Cardiotonic Agents , Chemistry , Pharmacology , Drug Design , Molecular Structure , Rats, Sprague-Dawley , Sodium-Hydrogen Exchangers , Structure-Activity RelationshipABSTRACT
In order to get some novel compounds with potent iNOS inhibitory activity, 12 target compounds of N-[ 4-( benzimidazole-2-thio) phenyl ] -N'-alkyl guanidine derivatives ( I1- I12 ) were synthesized from 1-benzoyl-3-[ 4-( benzimidazole-2-thio) phenyl] thioureas (4) by hydrolysis with 2. 0 mol x L(-1) sodium hydroxide solution containing tetrahydrofuran to form the corresponding N-[ 4-(benzimidazole-2-thio) phenyl] thioureas (5) which was S-ethylated with ethyl iodide, followed by amination with primary amines or secondary amines. The intermediate 4 was synthesized from 2-mercaptobenzimidazole (1) by reaction with 1-chloro-4-nitrobenzene to form 2-( 4-nitrophenylthio) benzimidazole (2) which was reduced by iron powder and hydrochloric acid, followed by reaction with benzoyl isothiocyanate. The structures of compounds I1 - I12 were confirmed by IR, MS,1H NMR and elemental analysis. The results of preliminary pharmacological test showed that the activities of three compounds (I 1, I8 and I10) were stronger than aminoguanidine, especially for compound I1.
Subject(s)
Animals , Mice , Benzimidazoles , Chemistry , Pharmacology , Cells, Cultured , Dose-Response Relationship, Drug , Enzyme Inhibitors , Chemistry , Pharmacology , Guanidines , Chemistry , Pharmacology , Macrophages, Peritoneal , Cell Biology , Molecular Structure , Nitric Oxide Synthase Type II , MetabolismABSTRACT
<p><b>AIM</b>To synthesize a series of 2-arylimino-4-thiazolidone derivatives and 2-imidazolino [2,3-b]-4-thiazolidone in order to get some novel potent compounds with nitric oxide synthases (NOS) inhibitory activity.</p><p><b>METHODS</b>The target compounds were prepared by reaction of N-chloroacetyl-1,2,3,4-tetrahydroisoquinoline or N-chloroacetylphthalimide with substituted thioureas, their NOS inhibitory activity were measured.</p><p><b>RESULTS AND CONCLUSION</b>The 15 new compounds were synthesized and most of the reaction yields were over 65%. The structures of new compounds were identified by IR, 1H NMR, MS and elemental analyses. Bioassay indicated that, most of 15 new compounds synthesized had confirmed bioactivities inhibition against NOS.</p>
Subject(s)
Molecular Structure , Nitric Oxide Synthase , Metabolism , Structure-Activity Relationship , Thiazoles , Chemistry , Pharmacology , ThioureaABSTRACT
<p><b>AIM</b>To search for novel compounds with potent nNOS inhibitory activity for the treatment of Alzheimer's disease.</p><p><b>METHODS</b>The target compounds were obtained by introducing benzenealkyl groups into the structure of isothioureas. nNOS inhibitory activity assays were conducted for the target compounds.</p><p><b>RESULTS</b>Sixteen benzenealkyl isothiourea compounds (I1-16) were synthesized by three different synthetic methods from benzylamine (1) or (substituted) phenethylamine (2). Compounds I1-6 were synthesized from 1 or 2 by reaction with benzoyl isothiocyanate to form the corresponding benzoylthioureas 3 or 4, followed by hydrolysis with 10% sodium hydroxide solution, then S-alkylation with methyl iodide or ethyl iodide. I7-14 were synthesized from 1 or 2 by reaction with methyl isothiocyanate to form the corresponding 1, 3-disubstituted thioureas 7 or 8 which were S-alkylated with methyl iodide or ethyl iodide. I15 and I16 were synthesized from 2 by reaction with dimethyl cyanodithioimidocarbonate. The structures of compounds I1-16 were confirmed by MS, IR, 1HNMR and elementary analysis. The results of preliminary pharmacological test showed that all compounds possessed nNOS inhibitory activity, among which compounds I8, I12 and I14 had good activity.</p><p><b>CONCLUSION</b>Compounds I8, I12 and I14 showed superior pharmacological profiles to the control compound S-methyl-N-(4-methoxyphenyl) isothiourea. The IC50 values of compounds I8, I12 and I14 inhibiting nNOS were 8.13 x 10(-7) mol.L-1, 1.74 x 10(-7) and 2.23 x 10(-7) mol.L-1 respectively, and it is worth further studying.</p>