Design, synthesis and biological evaluation of novel drugs for metabolic syndrome / 国际药学研究杂志

Objective To design and synthesize novel drugs for metabolic syndrome. Methods A kind of drugs treating metabolic 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 obtained by coupling acipimox with these primary amine intermediates, and their hypolipidaemic activity in Triton WR-1339 induced hyperlipi daemic mice was evaluated. Results and Conclusion 5 target compounds were synthesized and identified by1H 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.

Pulmonary fungal infections after bone marrow transplantation: the value of high-resolution computed tomography in predicting their etiology / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The correct diagnosis of etiology of fungal infection after bone marrow transplantation is very important to the choice of antifungal drugs and a premise for improvement of therapeutic efficacy. This study aimed to compare high-resolution computed tomography (HRCT) findings of the pulmonary fungal infections to determine whether the etiology of various fungal infections could be diagnosed with HRCT.</p><p><b>METHODS</b>Eighty-five cases were enrolled. According to the pathogens responsible for fungal infections, the patients were classified into three groups including invasive aspergillosis (n = 52), candidiasis (n = 19) and cryptococcosis (n = 14) groups. All the patients underwent HRCT scans. Two independent radiologists retrospectively analyzed the HRCT scans regarding CT patterns and distribution of lung abnormality.</p><p><b>RESULTS</b>Most fungal infections in the three groups occurred in the neutropenic phase. There was no significant difference in the constituent ratio of fungal infections at different phases after bone marrow transplantation among the three groups. Agreement between the two observers for all the CT characteristics of fungal infections was excellent (k > 0.75). There was a significant difference in occurrence ratio of mass among the three groups (P = 0.02). Occurrence ratio of mass (43.3%, 13/30) in the group with invasive aspergillosis was higher than in each of other two groups (20.0%, 2/10; 14.3%, 1/7). There was no significant difference in other CT characteristics of nodules or masses; including number, margin, halo sign, cavitation and air-crescent sign. There was no significant difference in number, margin, air bronchogram and distribution of air-space consolidation.</p><p><b>CONCLUSIONS</b>The HRCT appearance of various pulmonary fungal infections has a great deal of overlap and is nonspecific. Mass is more common in invasive aspergillosis, which is helpful to the diagnosis of invasive aspergillosis after bone marrow transplantation.</p>

Synthesis and antifungal activity of novel triazole antifungal agents / 药学学报

<p><b>AIM</b>A series of triazole antifungal agents were synthesized to search for novel triazole antifungal agents with more potent activity, less toxicity and broader spectrum.</p><p><b>METHODS</b>Twenty-one 1-(1H-1, 2, 4-triazolyl)-2-(2, 4-diflurophenyl)-3-(4-substituted-1-piperazinyl)-2-propanols were synthesized, on the basis of the three dimensional structure of P450 cytochrome 14alpha-sterol demethylase (CYP51) and their antifungal activities were also evaluated.</p><p><b>RESULTS</b>Results of preliminary biological tests showed that most of title compounds exhibited activity against the eight common pathogenic fungi to some extent and the activities against deep fungi were higher than that against shallow fungi. In general, phenyl and pyridinyl analogues showed higher antifungal activity than that of the phenylacyl analogues.</p><p><b>CONCLUSION</b>Several title compounds showed higher antifungal activities than fluconazole and terbinafine. Compound VIII-1, 4, 5 and IX-3 showed the best antifungal activity with broad antifungal spectrum and were chosen for further study.</p>

Synthesis and antifungal activity of 1-(1,2,4-triazolyl-1H-1-yl)-2-(2,4-diflurophenyl)-3-(4-substituted benzyl-1-piperazinyl)-2-propanols / 药学学报

<p><b>AIM</b>A series of triazole antifungals were synthesized to search for novel triazole antifungals with more potent activity, less toxicity and broader spectrum.</p><p><b>METHODS</b>Nineteen 1-(1,2,4-triazolyl-1H-1-yl)-2-(2,4-diflurophenyl)-3-(4-substituted benzyl-1-piperazinyl)-2-propanols were designed and synthesized, on basis of the three dimensional structure of P450 cytochrome 14 alpha-sterol demethylase (CYP51) and their antifungal activities were also evaluated.</p><p><b>RESULTS</b>All the title compounds were first reported. Results of preliminary biological tests showed that most of the title compounds exhibited high activity against the eight common pathogenic fungi and the activities against deep fungi were higher than that against shallow fungi.</p><p><b>CONCLUSION</b>Most of the title compounds showed higher antifungal activities than Fluconazole and Terbinafine. Compound VIII-1, 10, 12, 17 showed best antifungal activity with broad antifungal spectrum and were chosen for further development.</p>

Whole-liver MR perfusion imaging in rabbit liver VX_2 tumors:early findings of coagulative necrosis after percutaneous ethanol injection therapy / 中华放射学杂志

Objective To investigate the value of whole-liver MR perfusion imaging(MRPI)for early detection of coagulative necrosis after percutaneous ethanol injection(PEI)in rabbit liver VX_2 tumors. Methods VX_2 tumor cell suspension was inoculated into rabbit liver and liver VX_2 tumors[diameter of (2.6?0.6)cm]were induced in 10 male rabbits.MR T_1 WI and T_2 WI were performed to monitor the development of the liver tumor on the 2~(nd)and 3~(rd)week after inoculation.Whole-liver MRPI was performed in the 10 rabbits with liver VX_2 tumors before and 6 days after PEI therapy(1.0 ml ethanol was injected into the most enhanced tumor region under CT guiding).Signal intensity(SI)values of untreated tumor parts and treated areas 6 days after PEI were recorded respectively.The steepest slope(SS)and bolus arrival time (TO)of SI-time curves were measured.The t-Student test was used in statistical analysis of the data.Results There was significant difference in MRPI data between untreated tumor parts[TO:(16.0?1.2)s and SS: 38.9?2.2]and treated areas[TO:(50.8?5.9)s and SS:6.0?1.2]6 days after PEI(t was 15.8 and -39.6 respectively,P