A series of novel 4-substituted-3-nitrobenzamide derivatives were designed and synthesized. The structures of the target compounds were confirmed with 1H NMR, 13C NMR, MS and element analysis. Anti-tumor activities against HCT-116, MDA-MB435 and HL-60 cell lines in vitro were evaluated by SRB assay. The results indicated most of the target compounds exhibited potent anti-tumor activity. Compound 4a showed the most potent inhibitory activities against three cancer cell lines with the GI50 values of 1.904-2.111 micromol x L(-1). Compounds 4g, 41-4n exhibited more potent inhibitory activities against MDA-MB435 and HL-60 cell lines with the GI50 values of 1.008-3.586 micromol x L(-1) and 1.993-3.778 micromol x L(-1), respectively. The structure-activity relationship of these compounds is discussed preliminarily.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Benzamides ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Drug Design ; HL-60 Cells ; Humans ; Inhibitory Concentration 50 ; Structure-Activity Relationship

Objective To investigate the effect and mechanism of calcitonin(CT) in glutamate release from primary cultured neurons of midbrain periaqueductal gray matter(PAG).Methods Primary dissociated culture of PAG neurons was prepared from neonatal Sprague-Dawley (SD) rats.The cultured cells were divided into 4 groups:control group,salmon calcitonin (sCT) group,CT antagonist group (sCT8-32),and protein kinase C (PKC) inhibitor chelerythrine(Che) group.Each group was further divided into subgroups representing low,middle,and high levels of drugs.Glutamate release from the cultured PAG neurons evoked by sCT and/or other interfering factors was detected by using high-performance liquid chromatography (HPLC) assay.Results (1) Compared with the control group,sCT group yielded a time-dependent and concentration-dependent glutamate release from the cultured PAG neurons,and the most effective concentration of sCT was 20 nmol/L(P＜0.01).(2) sCT8-32,a selective antagonist of CT receptor,significantly reversed the effect of 20 nmol/L sCT on glutamate release from cultured PAG neurons,and the most effective concentration was 100nmol/L sCT8-32 (P＜0.01).(3) Incubation of the cultured neurons with Che inhibited the glutamate release from cultured PAG neurons evoked by 20 nmol/L sCT,and 100 μmol/L Che was most effective(P＜0.01).Conclusion CT receptors participates in the glutamate release from PAG neurons in which intracellular protein kinase C signaling pathway is involved.

Objective To investigate the influence of factors related to metabolic syndrome(MS)on the outcome in subjects without diabetes mellitus in a community.Methods A two-year follow-up study was conducted in 885 subjects who were enrolled in the epidemiologic survey carried out in Pingliang Community, Shanghai in 2002.Oral glucose tolerance test,lipid prefde,blood pressure(BP),body mass index(BMI),waist and hip circumferences were measured.Results (1)The baseline of BMI,fasting plasma glucose(FPG),2h plasma glucose after glucose loading(2hPG),BP,triglyceride(TG)in the subjects with impaired glucose regulation(IGR)increased significantly as compared to those with normal glucose regulation(NGR)(all P

Objective To explore the pathologic changes in the brain areas corresponding to specific cognitive function and underlying mechanism of cognitive impairment in patients with epilepsy by DTI study.Methods Forty-four Patients and 20 control subjects received the test of Wechsler Adult Intelligence Scale and the Diffusion-Tensor Imaging examination.Mean diffusivity (MD) and fractional anisotropy (FA) in the normal appearing white matter of interested area were measured.T test was employed to compare the MD and FA between patients and healthy controls,patients with normal and impaired FIQ respectively.The relationships between FIQ and DTI value were analyzed by Bivariate correlations.Results VIQ (100.52?17.63),PIQ (95.10?16.72) and FIQ (98.19?17.76) of the patients with epilepsy were significantly lower than those of health controls (VIQ,PIQ and FIQ were 109.77?13.54,108.11? 12.17 and 109.81?10.57,respectively).Significant reduction of FA in both side of posterior limb of internal capsule (P

Activation of microglia plays a vital role in the initiation and maintenance of specific neuropathic pain states. By activating microglia in central nervous system, Toll-like receptor 4 (TLR4) can promote the release of proinflammatory cytokines and neuroactive compounds, participate in the initiation and maintenance of neuropathic pain, and trigger the opiate side effects. Therefore, TLR4 may be a potential therapeutic target for neuropathic pain. Inhibition of TLR4 has shown some biological effects in neuropathic pain models and ibudilast (the TLR4 pathway-inhibiting agent) has been approved for for phase 2 clinical trials. This article briefly reviews the structure, function, and mechanism of TLR4 as well as the development of TLR4-targeted drugs.
Humans ; Neuralgia ; drug therapy ; physiopathology ; Toll-Like Receptor 4 ; antagonists & inhibitors ; physiology

A series of [1,3]dioxolo[4,5-f]isoindolone derivatives were designed, synthesized and evaluated as inhibitors of acetylcholinesterases (AChE). Furthermore, their effects on memory impairment of mice induced by scopolamine were investigated with step-through test. The results suggested that most of the target compounds exhibited potential inhibition on AChE with IC50 values at micromolar range. Compounds I1 (IC50 value of 0.086 μmol · L(-1)) and I2 (IC50 value of 0.080 μmol · L(-1)) showed the strongest AChE inhibitory activity, which are equipotent to donepezil (IC50 value of 0.094 μmol · L(-1)). Moreover, compounds I1-I4 could improve the memory impairment induced by scopolamine in mice.
Animals ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; Dioxoles ; chemical synthesis ; chemistry ; Drug Design ; Indans ; Inhibitory Concentration 50 ; Isoindoles ; chemical synthesis ; chemistry ; Memory Disorders ; drug therapy ; Mice ; Piperidines ; Scopolamine Hydrobromide

Patellofemoral arthritis is a clinical common type of knee osteoarthritis distinguished by its pain and anatomical position. The stability of patella is crucial to the stability of the patellofemoral joint and is related to the occurrence and development of osteoarthritis. Patella stability depends on the structural geometry of patellofemoral condyle, the static mechanics of the surrounding joint capsule, tendon, fascia, ligament and patellar ligament and the dynamic mechanics of the quadriceps. Therefore, manipulation therapy should be based on the considerations on the stability of the patella as well as TCM theory. Starting from maintaining the balance of the dynamic and static mechanical system and focusing on the restoration of the stability of patella, the ultimate goal of the treatment is to restore the stability of patellofemoral joint. The main aspects of manipulation treatment strategy include the balancing of dynamic and static mechanical system, the idea of holism treatment, differentiation treatment based on tendons injury identification, fundamental principle of softening tendons, cooperation between doctors and patients, and combination of therapy and convalesce.

Neck type cervical spondylosis, as one of the common types of cervical spondylosis, is a frequently occurring disease in orthopedics. The underlying pathogenetic basis is deficiency of positive qi (zhengqi). The disease is usually triggered by external contraction of cold in the neck area. The main clinical symptoms include pain in the occipital region, stiff neck and limitation of neck motion. Tuina (massage) is an effective treatment for this disease. It is effective in relieving symptoms as well as eliminating the underlying cause of the disease through warming yang and strengthening body resistance, regulating qi, and diagnosing and treating according to muscle and tendons conditions, and then address both the symptoms and root causes.

AIMTo exploit the characteristic digital criterion for the potential information characteristics of traditional Chinese medicine chromatographic fingerprints, the 37 parameters such as F and I were firstly proposed to disclose the potential information characteristics of traditional Chinese medicine fingerprints.

METHODSThe HPLC fingerprints of the Ginkgo biloba extract (GBE) , Ginkgo leaf extract and diphyridamole injection (GLEDI), Ixeris sonchifolia Hance (ISH) and Ixeris sonchifolia Hance injection (ISHI) were compared each other.

RESULTSAs far as the peak signal intensity, the uniform of peak signal, resolution and the fingerprint information were concerned. The GBE fingerprint was better than the GLEDI's, and the ISH fingerprint was also better than the ISHI's, then GBE fingerprint was close to the ISHI' s.

CONCLUSIONThe 37 parameters such as F and I can be used to objectively, authentically and thoroughly display the potential information characteristics of the traditional Chinese medicine chromatographic fingerprints.

Asteraceae ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Ginkgo biloba ; chemistry ; Medicine, Chinese Traditional ; Plant Leaves ; chemistry

OBJECTIVETo study the regulatory effect of Bushenfang on the serum testosterone (T) level of naturally aging rats and its mechanism, in order to provide a theoretical and experimental basis for the clinical treatment of late onset hypogonadism (LOH) in males.

METHODSThirty-two 18-month-old male SD rats were randomly divided into four groups of equal number, naturally aging model and low-, medium- and high-dose Bushenfang groups, and another eight 4-month-old rats were taken as normal controls. The rats of the aging model and normal control groups were treated with normal saline, while those of the low-, medium- and high-dose Bushenfang groups received intragastrically Bushenfang at 3.25, 7.50 and 15.00 g/kg, respectively, all for 3 weeks. Then the rats were sacrificed, the histomorphologic changes of the testis observed by HE staining, the serum T level measured by radioimmunoassay, and the expressions of the StAR protein, P450scc and 3beta-HSD I determined by RT-PCR.

RESULTSThe number of Leydig cells was obviously increased after Bushenfang treatment. The levels of serum T were significantly higher in the low-, medium- and high-dose Bushenfang groups ([6.74 +/- 1.56] nmol/L, [8.50 +/- 1.99] nmol/L and [12.41 +/- 2.91] nmol/L) than in the model group ([3.48 +/- 0.75] nmol/L) (P < 0.05). The three Bushenfang groups also showed a remarkable elevation in the mRNA expressions of StAR (0.74 +/- 0.29, 0.83 +/- 0.32 and 1.35 +/- 0.50), P450scc (0.72 +/- 0.36, 1.023 +/- 0.30 and 1.41 +/- 0.37) and 3beta-HSD I (0.58 +/- 0.14, 0.72 +/- 0.07 and 0.85 +/- 0.18), as compared with the models (StAR: 0.44 +/- 0.09; P450scc: 0.33 +/- 0.05; 3beta-HSD I: 0.34 +/- 0.02), with significant differences in the StAR expression between the high-dose Bushenfang and the model groups, as well as in P450scc and 3beta-HSD I expressions between the medium- and high-dose Bushenfang and the model groups (P < 0.05).

CONCLUSIONBushenfang could improve the pathological status of testicular injury and increase the expression of testosterone synthetase, which might be the mechanism behind its regulatory effect on the serum T level of aging rats.

Aging ; drug effects ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Hypogonadism ; drug therapy ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Testis ; drug effects ; Testosterone ; metabolism