Synthesis and anti-hepatocellular carcinoma activity of novel O-vinyl diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid / 中国天然药物

Considering that high levels of nitric oxide (NO) exert anti-cancer effect and the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity, new O-vinyl diazeniumdiolate-based NO releasing derivatives (5a-l, 11a-l) of OA were designed, synthesized, and biologically evaluated in the present study. These derivatives could release different amounts of NO in liver cells. Among them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and displayed stronger proliferative inhibition against SMMC-7721 and HepG2 cells than OA and other tested compounds. The most active compound 5j showed almost 20-fold better solubility than OA in aqueous solution, released larger amounts of NO in liver cancer cells than that in normal ones, and exhibited potent anti-hepatocellular carcinoma activity but little effect on the normal liver cells. The inhibitory activity against the cancer cells was significantly diminished upon addition of an NO scavenger, suggesting that NO may contribute, at least in part, to the activity of 5j.

Synthesis and antibacterial activity of imidazothiadiazoles and heterocyclic-amine Mannich-base hydrochloride / 药学学报

To optimize the synthetic method and antibacterial activity of fused heterocyclic thiadiazole compounds, cyclocondensation of 2-(4-methoxyphenyl)-5-amino-1,3,4-thiadiazole (2) with alpha-chloro-4-chloro acetophenone (3) resulted in a key intermediate (4), 6 -(4-chlorophenyl)-2-(4-methoxyphenyl)-imidazo-[2,1-b][1,3,4]thiadiazole, which was carried out an nucleophilic substitution with substituted piperazine to give the corresponding free bases of piperazine (5a-5c), then followed by Mannich reaction with heterocyclicamines and formaldehyde to yield the corresponding Mannich bases, (1a-11) as respective hydrochloride salts. The structures were confirmed by IR, 1H NMR, MS and elemental analysis and the antibacterial activities in vitro of fifteen newly synthesized compounds were also tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method. The antibacterial results showed that the introduction of a polar group resulted in the enhancement of antibacterial activity in vitro. Thus, the structures of these fused compounds could further be investigated.

Synthesis and antitumor activity of C3 heterocyclic-substituted fluoroquinolone derivatives (I): ciprofloxacin aminothiodiazole Schiff-bases / 药学学报

To discover a novel antitumor lead compound derived from fluoroquinolone, C3 carboxyl group of ciprofloxacin (1) was replaced with heterocyclic ring to form cyclopropyl fluoroquinolone aminothiadiazole scaffold (2), then reacted with aromatic aldehydes to give the Schiff bases compounds (3a-3j). The structures of new compounds were characterized by element analysis and spectral data, and their in vitro antitumor activity against SMMC-7721, HL60 and L1210 cell lines was evaluated by MTT assay via the respective IC50 values. The bioactive assay showed that eleven thiadiazole-substituted ciprofloxacin derivatives displayed potential cytotoxicity against the tested cancer cell lines, where the IC50 values of compounds 3d and 3f reached micromolar concentration. Therefore, the C3 carboxyl group of fluoroquinolone is not necessary to antitumor activity. Functionally modified heterocycle-substituted fluoroquinolone as potent antitumor lead compound is valuable for further study.

Synthesis and antibacterial activity of 3-(4-piperazin-1-yl-phenyl)-s-triazolo 3,4-b 1,3,4 thiadiazole hydrochlorides / 药学学报

To study the synthetic method and antibacterial activity of water-soluble fused heterocyclic compounds containing piperazine group, the nucleophilic substitution of 3-(4-chlorophenyl)-6-substituted-s-triazolo-[3, 4-b] [1, 3, 4] thiadiazoles (2a - n) with piperazine in the presence of phase transfer catalyst TBAI afforded 3-(4-piperazin-1-yl-phenyl)-6-substituted-s-triazolo [3, 4-b] [1, 3, 4] thiadiazole and then followed by acid treatment afforded 3-(4-piperazin-1-yl-phenyl)-6-substituted-s-triazolo [ 3, 4-b] [1, 3, 4] thiadiazole hydrochlorides (3a - n). Twenty-eight new compounds were synthesized and their structures were confirmed by IR, 1H NMR, MS and element analysis. The in vitro antibacterial activities of all newly synthesized compounds were tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method. Fourteen title compounds exhibited potential antibacterial activities in vitro. The structures of these compounds needed to be further optimized.

Synthesis and vascular relaxing activity of arecoline derivatives coupled with nitric oxide donors / 药学学报

<p><b>AIM</b>To search for potential anti-atherosclerosis drugs with vascular relaxation activity, a series of agonists of endothelial targets were designed and synthesized.</p><p><b>METHODS</b>Coupling N-methyl-1,2, 3,6-tetrahydrapyridine ring system with 3,4-dibenzenesulfonyl-1,2,5-oxadiazole-2-oxide through esterification or amidation, a series of arecoline derivatives containing NO donors were designed and synthesised.</p><p><b>RESULTS</b>A novel series of compounds structurally related to arecoline have been prepared, the proposed structures of eighteen new compounds were established by IR, 1H NMR, MS spectroscopy and elemental analysis. The effects of the target compounds on the vasodilation activity were tested in the isolated preparation of mice thoratic aorta.</p><p><b>CONCLUSION</b>This preliminary pharmacological tests showed that the candidates have good vasodilation activities and were worthy to be intensively studied.</p>

Synthesis and antibacterial activity of 3-(4-amino-5-methyl-s-triazol-3-sulfanyl)-1-phenyl-propan-1-one O-(5-substituted phenyl-1,3,4 oxadiazol-2-methyl)-oximes / 药学学报

<p><b>AIM</b>To study the synthetic method and antibacterial activity of amino-heterocyclic compounds coupled oxime-ether group.</p><p><b>METHODS</b>The treatment of 4-amino-3-methyl-5-mercapto-s-triazole (3) with beta-chlorophenyl-propanone to form amino-s-triazole sulfanylphenyl-propanone (4) sequentially followed by oximation with hydroxyl-amine to produce the oximes (5) and etherification with various oxadiazole chloromethanes (6a - j) to yield the title compounds (1a - j). The in vitro antibacterial activities of all newly synthesized compounds were tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method.</p><p><b>RESULTS</b>Twelve new compounds including two intermediates were synthesized and their structures were confirmed by IR, 1H NMR, MS and elemental analyses. The ten title compounds exhibited the potential antibacterial activities in vitro.</p><p><b>CONCLUSION</b>Theses compounds should be optimized.</p>

Synthesis and antibacterial activity of 3-(5-substituted phenyl-1,3,4 oxadiazole-2-yl-methylenethio)-5-pyridin-3-yl-1,2,4 triazole-4-yl-amines / 药学学报

<p><b>AIM</b>To study on synthesis and antibacterial activity evaluation of polyheterocycles.</p><p><b>METHODS</b>The condensation of 4-amino-3-pyridin-3-yl-4H-[1,2,4] triazole-5-thiol with 2-chloromethyl-5-substituted phenyl-[1,3,4] oxadiazoles gave the corresponding title heterocycle amines, and the in vitro antibacterial activity was primarily evaluated by the method of cup-plate diffusion solution.</p><p><b>RESULTS</b>Twelve novel compounds were synthesized, and their structures were confirmed by IR, 1H NMR, MS and element analysis. Biological screening results demonstrated that most of the compounds prepared showed good antibacterial activity.</p><p><b>CONCLUSION</b>Oxadiazoles incorporting pyridyl triazole ring may be a pharmacophor structure in the molecule for developing antibacterial candidate drugs.</p>

Synthesis and antibacterial activity of 2-(3-pyridyl)-5-((5-aryl-1,3,4-oxadiazol-2-yl) methylenethio)-1,3,4-oxadiazoles / 药学学报

<p><b>AIM</b>Studies on synthesis and antibacterial activity of new heterocycles.</p><p><b>METHODS</b>The cyclocondensation of [(3-pyridyl)-1,3,4-oxadiazol-2-yl] thio acetic acid with various aroyl hydrazines in the presence of POCl3 and xylene gave the corresponding titled compounds, and the in vitro antibacterial activity was primarily evaluated by the method of cupplate diffusion solution.</p><p><b>RESULTS</b>Sixteen novel titled compounds were synthesized, their structures were confirmed by IR, 1HNMR, MS and elemental analysis. Biological screening results demonstrated that most of the compounds prepared displayed potential antibacterial activity.</p><p><b>CONCLUSION</b>Oxadiazoles incorporting pyridyl oxadiazole ring may be usefully antibacterial candidate drugs.</p>

Synthesis and vasorelaxant activities of benzopyran-4-one hydrazone derivatives / 药学学报

<p><b>AIM</b>In search of more potent, less toxic and selective potassium channel openers.</p><p><b>METHODS</b>According to the structure-activity relationships of benzopyran compounds and the features of structures of aprikalim, dofetilide and nifekalant, twenty benzopyran-4-one hydrazone derivatives have been designed and synthesized from 4-cyanophenos through acetylation, Fries rearrangment, cyclization, hydrazone, substitution reaction and so on. The compounds were tested for their vasorelaxant activity in low (30 mmol.L-1) and high (80 mmol.L-1) KCl-induced contraction of rat aorta to identify potential potassium channel openers in vitro.</p><p><b>RESULTS</b>Three series of twenty benzopyran-4-one hydrazone derivatives, nominated N-aminoacetyl-(6-cyano-3,4-dihydrospiro [2H-1-benzopyran-2,1'-cyclohexane]-4)-one hydrazone (I), 2-(6-cyano-3, 4-dihydro-2H-1-benzopyran-4-ylene) hydrazinethiocarboxamide derivatives (II) and N-(2-arylethyl) aminoacetyl-(6-cyano-3,4-dihydro-2H-1-benzopyran)-4-one hydrazone (III), have been synthesized. They (I1-9, II1-4 and III1-7) are new compounds. Their chemical structures were determined by IR, 1HNMR, MS and elemental analysis. The vasorelaxant effects of those novel compounds indicated that some of the compounds have vasorelaxant activities at 1 x 10(-6) mol.L-1.</p><p><b>CONCLUSION</b>The vasorelaxant activities of compounds I9, III2 and III5 in inhibiting low KCl-induced vasocontraction at 1 x 10(-6) mol.L-1 are less potent than the reference compound emakalim. However they are more potent than emakalim to inhibition high concentration KCl-induced vasocontraction at 1 x 10(-5) mol.L-1. It is worthy of further study.</p>