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Chinese Chemical Letters 2010年第6期 661-663页

作者： guo qiang hu~(a,*),zhong quan zhang~a,song qiang xie~a,wen long huang~b a institute of chemistry & biology,henan university,kaifeng 475001,china b china pharmaceutical university,nanjing 210009,china

Five C3/C3 fluoroquinolone dimers tethered with a fused heterocyclic ring of s-triazolo[2,1-b][1,3,4]thiadiazole derived from antibacterial quinoiones were synthesized and characterized,and their in vitro antitumor ac... 详细信息

关键词： Fluoroquinolone Dimer Antitumor evaluation

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun guo Yi Su Yu-Ya-Nan zhang Hao Yu Zhe Lu wen-qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li bing Liu Hai-Liang huang Lu-Xian Lv Yin Yao Yun-long Tan Gerome breen Ian Everall Hong-Xing Wang Zhuo huang Dai zhang Wei-hua Yue institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC Key Laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking university huilongguan Clinical Medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina henan Key Lab of biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina Key Laboratory of Animal Models and human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of biostatistics and Computational biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Natural and biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern institute for brain Research Peking UniversityBeijing 100871China Chinese institute for brain Research Beijing 102206China

background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(LINC01795,DDHD2,SbNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

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Synthesis and antitumor evaluation of fluoroquinolone C3 fused heterocycles(Ⅱ):From triazolothiadiazines to pyrazolotriazoles

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Chinese Chemical Letters 2011年第7期22卷 804-806页

作者： guo qiang hu Li Li Hou Yong Yang Lei Yi song qiang xie guo qiang Wang Nan Nan Duan Tie Yao Chao Xiao Yi wen wen long huang institute of chemistry & biology Henan University Kaifeng 475001 China china pharmaceutical university Nanjing 210009 China

To further expand an effective modified route for the shift from an antibacterial fluoroquinolone （FQ） to an antitumor FQ, two series of title compounds based on an isostere of the FQ C3 carboxylic group with two fused heterocyclic rings, [ 1,2,4]triazolo[3,4- b][1,3,4]thiadiazine and pyrazolo[5,1-c][1,2,4]triazole, respectively, were designed and synthesized starting from the current antibacterial FQs, and their in vitro antitumor activity against L1210, CHO cell lines were evaluated via their respective IC50 values.

关键词： Fluoroquinolone Triazolothiadiazine Pyrazolotriazole Antitumor evaluation

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Design, synthesis and antitumor activity of C3/C3 bis-fluoroquonolones cross-linked with [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazole

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Acta Pharmaceutica Sinica b 2011年第3期1卷 172-177页

作者： guo-qiang hu Yong Yang Lei Yi guo-qiang Wang Nan-nan Duan Xiao-yi wen Tie-yao Cao song-qiang xie wen-long huang institute of chemistry&biology Henan UniversityKaifeng 475001China Center of Drug Discovery China Pharmaceutical UniversityNanjing 210009China

To contribute to the development of an efficient method for the conversion of antibacterial fluoroquinolones to antitumor fluoroquinolones,a series of C3/C3 bis-fluoroquinolone fused heterocycles cross-linked with a[1,2,4]-triazolo[3,4-b][1,3,4]-thiadiazole core as a common bioisostere of two carboxylic acid groups was designed and synthesized as their hydrochloride *** were characterized by elemental analysis and spectral data and their in vitro antitumor activity against L1210,CHO and HL60 cell lines was screened by determination of their IC50 values in the methylthiazole trazolium(MTT)*** compounds were highly potent against the HL60 cell line and represent promising lead compounds for future development.

关键词： Fluoroquinolone Triazolothiadiazole Synthesis Antitumor evaluation

Limitation standard of toxic aconitines in Aconitum proprietary Chinese medicines using on-line extraction electrospray ionization mass spectrometry

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Acta Pharmaceutica Sinica b 2020年第8期10卷 1511-1520页

作者： Zi-Dong Qiu Xu-Ya Wei Rui-Qi Sun Jin-long Chen Ting Tan Jia-quan Xu Guang-Hong Cui Tong Chen Juan guo Chang-Jiang-Sheng Lai Lu-Qi huang State Key Laboratory breeding base of Dao-di Herbs National Resource Center for Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China The National pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine Jiangxi University of Traditional Chinese MedicineNanchang 330006China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation College of ChemistryBiology and Material SciencesEast China Institute of TechnologyNanchang 330013China

Development of rapid analytical methods and establishment of toxic component limitation standards are of great importance in quality control of traditional Chinese medicine. Herein, an online extraction electrospray ionization mass spectrometry(oEESI-MS) coupled with a novel whole process integral quantification strategy was developed and applied to direct determination of nine key aconitine-type alkaloids in 20 Aconitum proprietary Chinese medicines(APCMs). Multi-type dosage forms(e.g., tablets, capsules, pills, granules, and liquid preparation) of APCM could be determined directly with excellent versatility. The strategy has the characteristics of high throughput, good tolerance of matrix interference, small amount of sample(~0.5 mg) and reagent(~240 μL) consumption, and short analysis time for single sample(be credible by high performance liquid chromatographyàmass spectrometry(LC-MS) and electrospray ionization mass spectrometry, respectively. Moreover, the limitation standard for the toxic aconitines in 20 APCMs was established based on the holistic weight toxicity(HWT) evaluation and the Chinese Pharmacopoeia severally, and turned out that HWT-based toxicity evaluation results were closer to the real clinical applications. Hence,a more accurate and reliable APCM toxicity limitation was established and expected to play an important guiding role in clinics. The current study extended the power of ambient MS as a method for the direct quantification of molecules in complex samples, which is commonly required in pharmaceutical analysis,food safety control, public security, and many other disciplines.

关键词： Aconitum dosage tablets

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