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Objective To design and synthesize novel drugs for metabolic syndrome. Methods A kind of drugs treating met?abolic syndrome was designed by linking acipimox with the lipid lowering function group of fibrates. Primary amine intermediates were synthesized from 4-aminophenol,4-(aminomethyl)phenol and 4-(2-aminoethyl)phenol by 3 steps,then target compounds were ob?tained by coupling acipimox with these primary amine intermediates,and their hypolipidaemic activity in Triton WR-1339 induced hy?perlipi daemic mice was evaluated. Results and Conclusion 5 target compounds were synthesized and identified by 1H NMR and ESI MS methods. It showed that all the compounds could decrease blood-lipid,and 4c exhibited anti-hyperlipidemic activities close to the positive control(bezafibrate)in in vivo hypolipidemic activity tests. The results have good value for the discovery of novel drugs for metabolic myndrome.
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Objective To improve the in vivo analgesic activity of acacetin and find leads for the development of new drugs, novel acacetin derivatives containing alkyl amide groups with different length of carbon chain were designed and synthesized according to the molecular structure of the active hit compound found in our previous work. Methods Using apigenin as the initial chemical ma-terial,the acacetin was synthesized through 3 steps,then the target compounds were prepared by conjugating hydroxy group of acace-tin at position 7 with bromoalkyl amides. The analgesic activity of the target compounds was evaluated by acetic acid writhing model of mice. Results and Conclusion Novel acacetin alkyl amide derivatives showed more potent analgesic activities than that of clinical medicine diclofenac,which could be used as leads for further development of new drugs.
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Natural product resveratrol has antioxidation,cardiovascular protection and many other useful biological activities. In recent years,many researchers have paid more and more attention to it. However it cannot be used as candidate for the development of new drug due to its poor druggability. Novel resveratrol derivates with improved water solubility and highly potent biological activity could be obtained by chemical modifying of chemical structure of resveratrol. Researches have shown that resveratrol derivatives exhib?it many kinds of attractive activities,including antitumor,reducing blood fat,antiviral,anti-neurodegenerative diseases and so on, which makes them could be used as leads for the further developing of new drugs. This review discusses the development of novel resve?ratrol derivatives by chemical modification in recent years..
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HIV-1 fusion inhibitors are a new class of anti-HIV compounds, which block the entry of HIV into target cells through preventing the fusion between viral and cell plasma membrane and thus interrupt the initial steps of viral replication. T-20 (enfuvirtide), which has been clinically approved as the first fusion inhibitor of HIV-1 by U.S. FDA in 2003, can suppress replication of HIV variants with multi-drug resistance to reverse transcriptase and protease inhibitors. Peptides and small molecules display potent anti-HIV fusion activities by targeting gp41 thus inhibit its fusogenic function. In recent years, with the development of studies on the molecular mechanism of HIV membrane fusion process and the function of gp41, many new fusion inhibitors are found and some have been in advanced clinical trials. This review discusses recent progress in the development of HIV-1 fusion inhibitors targeting the gp41.
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In medical organic chemistry education, seven design method of introduction are put forward by using teaching art in educational segment, allowing students to enhance the study activity in lively atmosphere.
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Objective To investigate the effects of the left ventricular geometry on left atrial structure and function in essential hypertension (EH).Methods One hundred and thirty-eight patients with EH and 86 normal controls were studied with echocardiography.According to left ventricular mass index (LVMI) and relative wall thickness (RWT),a total of 138 patients with EH were divided into normal geometry group (58 cases),concentric remodeling group (22 cases),concentric hypertrophy group (21 cases) and eccentric hypertrophy group (37 cases).Correlation between left atrial diameter index (LADI),left atrial ejection force (LAEF) and all parameters was respectively obtained using linear regression analysis,and the stepwise regression analysis was used to assess the independent effect of each parameter.Results Compared with control group,LADI and LAEF were higher ( P
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Pulsed wave Doppler echocardiograpdy was performed in eighteen cases with chronic mitral regurgitation(CMR)and 21 normal individuals td detect the quantitative changes of the mitral diastolic flow spectrum.The results showed that the pseudonormalization of mitral flow spectrum in CMR was actually caused by impaired left ventricle(LV)active relaxation and decreased LV compliance:It thus masked the LV diastolic dysfunction in CMR.E-wave pressure gradiant(E-PG),A-wave pressure gradiant(A-PG),isovolumic relaxation time(IVRT),E deceleration time(E-DT)and LV filling time(LVFT)in CMR group were significantly different in from those in normal group(P<0.01).Therefore it is essential to integrate these parameters as the indexes to evaluate the LV diastolic dysfunction in CMR.
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Objective:The immunological effects of HCV-DNA vaccine with different adjuvants were detected by ELISPOT in mice.Methods:Female BALB/c mice were primed with naked HCV-DNA, HCV-DNA encapsulated by liposome DDAB/EPC or DC-Chol/DOPE, HCV-DNA mixed with Montanide ISA 720 or aluminum hydroxide, respectively, and boosted twice accordingly in a four-week interval. Cytokine production by splenocytes was assessed by ELISPOT.Results:In most cases, splenocytes from mice vaccinated with DDAB/EPC liposome produced more IFN-?. These splenocytes also have significant higher IL-2 production compared with the other groups. In expansion with NS5b, splenocytes from alum group have significance in IL-4 production compared with other groups. The profile of cytokine production revealed that the INF-? overwhelmed IL-4 in naked DNA, DDAB/EPC, and DC-Chol/DOPE groups while IL-4 surmounted IFN-? in alum and Montanide groups.Conclusion:Encapsulation with liposome DDAB/EPC has the strongest adjuvant effect in inducing Th1 dominated immunity. Alum and Montanide can convert the Th1 nature of DNA vaccine to Th2-biased immunity.