Method for screening cysteinyl leukotriene receptor 2 antagonists and preliminary screening of compounds / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To establish a method for screening cysteinyl leukotriene receptor 2 (CysLT(2)) antagonists and to preliminarily screen a series of synthetic compounds.</p><p><b>METHODS</b>Rat glioma cell line (C6 cells) highly expressing CysLT(2) receptor was used. Intracellular calcium concentration was measured after stimulation with the agonist LTD(4),which was used to screen compounds with antagonist activity for CysLT(2) receptor. Bay u9773, a CysLT1/CysLT(2) receptor non-selective antagonist, and AP-100984, a CysLT(2) receptor antagonist, were used as control.</p><p><b>RESULT</b>PT-PCR showed a higher expression of CysLT(2) receptor in C6 cells. LTD(4) at 1 mumol/L significantly increased intracellular calcium in C6 cells; the maximal effect was about 37.5% of ATP, a positive stimulus.LTD(4)-induced increase of intracellular calcium was blocked by CysLT(2) receptor antagonists, but not by CysLT(1) receptor antagonists. Among the synthetic compounds, D(XW-)1,2,13,23,29 and 30 inhibited LTD(4)-induced increase of intracellular calcium.</p><p><b>CONCLUSION</b>LTD(4)-induced change in intracellular calcium in C6 cells can be used as a screening method for CysLT(2) receptor antagonists. The compounds, D(XW-)1,2,13,23,29 and 30, possess antagonist activity for CysLT(2) receptor.</p>

Recent advances in the study of bioreductive drugs targeted tumor hypoxia / 药学学报

Tumor hypoxia is the necessary process in the development of solid tumors, which is the key factor for drug resistance, recurrence, attack and shift of tumor. Hypoxic tumor cells have a certain extent of tolerance to radiation and chemotherapy. Tumor hypoxia is an important target for medication therapy. In the recent years, the bioreductive drugs targeted tumor hypoxia has made great process in the treatment of tumors. The latest advances of bioreductive drugs targeted hypoxia were reviewed in this paper.

Synthesis and AchE inhibitory activity of 2-phenoxy-indan-1-one derivatives / 药学学报

<p><b>AIM</b>To design and synthesize novel AchE inhibitors.</p><p><b>METHODS</b>The condensation of 2-bromo-5, 6-dimethoxy-indan-1-one with various aminoalkyl phenols in the presence of K2CO3 and acetonitrile gave the corresponding title compounds, and the in vitro AchE and BchE inhibitory activities were evaluated by the modified Ellman method.</p><p><b>RESULTS</b>Sixteen novel target compounds 8a - p were synthesized, their structures were confirmed by 1H NMR, MS, IR and elemental analysis. Preliminary pharmacological test demonstrated that most of these compounds displayed high AchE inhibitory activities, the IC50 of the most potent inhibitor 8h was 50.0 nmol x L(-1), similar to that of Huperzine A (IC50 = 53.0 nmol x L(-1)), while all the compounds were almost inactive against BchE.</p><p><b>CONCLUSION</b>2-Phenoxy-indan-1-one derivatives exhibit high activities of AchE inhibition and are worthy of further investigation.</p>

Synthesis and vasorelaxation action of flavonoids / 药学学报

<p><b>AIM</b>To search for flavonoids which possess stronger vasorelaxation action.</p><p><b>METHODS</b>Four quercetin glycosides (1a - d) were synthesized from quercetin in three steps i. e. selective protection of quercetin, condensation with corresponding acetyiglycosyl bromide, and then removal of the protecting group; Six flavone compounds (2a - f) were prepared from phloroglucinol according to the conventional methods; The structures of synthetic compounds were confirmed by IR, 1H NMR, 13C NMR and MS. Vasorelaxation action of ten synthetic quercetin derivatives (or analogues) and four natural flavonoids compounds were examined on the isolated rat thoracic aorta rings; Comparative octanol-water partition coefficients (logP) were measured using a reversed-phase HPLC method.</p><p><b>RESULTS</b>Most of the tested flavonoids showed concentration dependent relaxation effects against PE-induced contractions of rat aortic rings. These compounds had stronger action with the augment of logP values.</p><p><b>CONCLUSION</b>Compound 3-bromo-5 ,7-dihydroxyflavone (2d) was identified to have the most potent vasodilating action. These compounds exert vasodilating effects that are related to the logP values. A structure-activity relationship of flavonoids was suggested.</p>

Synthesis and antitumor activity of arylsubstituted imidazolin-2-one derivatives / 药学学报

<p><b>AIM</b>To design and synthesize new arylsubstituted imidazolin-2-one analogues as antitumor compounds.</p><p><b>METHODS</b>Arylsubstituted imidazolin-2-ones were prepared by condensation the appropriate omega-amino-acetophenone hydrochloride with arylisocyanate in toluene. The target compounds prepared in this study were tested for cytotoxicity against PC-3, A549, HO-8910, Hela, HL60, K562 and HL60R cancer cell lines, and mechanism of one of the products 4y was further evaluated with its mechanium.</p><p><b>RESULTS</b>Thirty-six new compounds were synthesized and confirmed by 1H NMR, MS and elemental analysis. One of the synthesized products, compound 4y, displayed an encouraging selective activity against HL60 cells, and it was partlydue to the cell cycle arrest and cell apoptosis.</p><p><b>CONCLUSION</b>Compound 4y is worthy to be intensively studied.</p>

An improved novel method of venlafaxine synthesis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To synthesize venlafaxine with an improved novel method.</p><p><b>METHODS</b>p-methoxypheny lethyl-acid was reacted with SOCl(2) to produce acyl chloride which was reacted with N,N-dimethylamine solution to get amide; then through Ivanov reaction and reduction by KBH(4)/BF(3).Et(2)O to yield venlafaxine.</p><p><b>RESULT</b>Venlafaxine was successfully synthesized by using this method with an yield rate of 50.3%.</p><p><b>CONCLUSION</b>The improved method is suitable for industrial production of venlafaxine.</p>

Study on ultrasonic extraction techniques of flavonoids in Chrysanthemum morifolium / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize the ultrasonic extraction condition for flavonoids from Chrysanthemum morifolium.</p><p><b>METHOD</b>The extraction rate of flavonoids optimized condition (ethanol concentration, ultrasonic time, solvent quantity and extraction times) was determined by orthogonal design. UV-Spectrophotometry was used for the determination.</p><p><b>RESULT</b>The order of factors to affect the flavonoid extraction was ethanol concentration > extraction times > solvent quantity > ultrasonic time.</p><p><b>CONCLUSION</b>The optimum ultrasonic extractions were: A2 B2 C3 D3. Compared with traditional extraction, ultraction method can save time, be easy to operate, improve extraction rates and need no heating.</p>

Study on extraction technology for extract and flavonoids in Chrysanthemum morifolium by orthogonal design / 中国中药杂志

<p><b>OBJECTIVE</b>To ascertain extraction technology condition for extract and flavonoids from Chrysanthum morifoliwn.</p><p><b>METHOD</b>The optimizing ultrasonic extraction condition on the basis of extractive yield and flavonoids were determined by orthogonal design.</p><p><b>RESULT</b>The order of factors which affected the flavonoid extraction was extraction times > ethanol concentration > ultrasonic time > solvent quantity.</p><p><b>CONCLUSION</b>The optimum ultrasonic extractions are A2B3C3D3. Compared with traditional extraction, ultraction method is timesaving, simple to operate, stable and need not be heated.</p>

Improved method of fluvoxamine synthesis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To modify the synthetic method of fluvoxamine.</p><p><b>METHODS</b>Fluvoxamine was synthesized from 4-trifluoromethylbenzonitrile by the steps of Grignard reaction, hydrolysis and oximation.</p><p><b>RESULT</b>The chemical structure of the synthesized product was confirmed by (1)HNMR, and the total yield reached to 36.16%.</p><p><b>CONCLUSION</b>The results indicate that the synthetic route is practical.</p>

Improved method of epalrestat synthesis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To synthesize epalrestat and to improve the method of synthesis.</p><p><b>METHODS</b>Glycine reacted with carbondisulfide,then with ClCH(2)COONa to give 3-carboxymethylrhodanine. PhCHO reacted with CH(3)CH(2)CHO in NaOH/EtOH solution to produce 2-methylcinnamaldehyde.3-carboxymethylrhodanine and 2-methylcinnamaldehyde were treated with NH(3).H(2)O to obtain epalrestat.</p><p><b>RESULT</b>The described method was effective in synthesis of Epalrestat and the yield was higher than that of in references.</p><p><b>CONCLUSION</b>The results suggest that this method is suitable for industrial production.</p>

Synthesis of hirsutrin and hyperin / 浙江大学学报·医学版

OBJECTIVE: To investigate an easier method for preparation of hirsutrin and hyperin. METHODS: Rutin was utilized as the starting material. The target compounds were produced via benzoylation, hydrolysis, glycosidation and deproteination. RESULTS: The yield of key intermediate 5,7,3',4'-tetra-O-benzoyl quercetin was improved by reducing the hydrolysis time of 5,7,3',4'-tetra-O-benzoyl rutin in HCl/EtOH. Hirsutrin and hyperin were synthesized. CONCLSION: Hirsutrin can be synthesized and the yield of hyperin improved by this method.

Preparation of albendazole sulfoxide--- an active metabolite / 浙江大学学报·医学版

OBJECTIVE: To investigate the facile method for preparation of albendazole sulfoxide, an active metabolite in vivo. METHODS: The reaction condition was investigated according to evaluations to the results of the experiment through temperature, solvent, oxidation agent, reaction time and impurity. RESULTS: The target compound was obtained by oxidation of albendazole with the presence of sodium metaperiodate in glacial acetic acid under low temperature and was free from contamination by impurity albendazole sulfone. Pure product (content >98%) and high yield (>90%percnt;) have been achieved due to reaction selection. CONCLUSION: Oxidation condition is essential to the preparation of albendazole sulfoxide.