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中文摘要：
本项目基于国际国内抗微生物药物研发的新形势，在申请人多年从事唑类化合物研究的基础上，利用药物设计拼合原理，参考药物发挥药效作用时利用多种非共价键力与靶分子形成生物超分子的结构特点，首次将含有多个官能团且具有不同作用靶点的一线临床抗细菌药物喹诺酮和三唑类抗真菌药杂合，设计合成一系列具有双作用靶点的新型喹诺酮三唑化合物，制备其金属络合物，模拟培养活性位点喹诺酮三唑-拓扑异构酶-DNA形成的生物超分子，进行喹诺酮三唑与DNA的结合、切割及DNA复制抑制等有关抗微生物作用机制研究，考察其抗微生物能力。这一系列原始创新性研究，有望获得拥有自主知识产权的抗微生物谱宽、高效的抗菌、抗真菌等强活性分子，为解决日趋严重的耐药性、顽固的致病性微生物以及新出现的有害微生物的临床治疗提供新候选药物分子。此类源头上创新药物研究课题，对国民经济和社会发展及人民健康等都将具有重要的理论价值和实际意义。
英文摘要：
Quinolone；1,2,4-triazole；supermolecule；antibacterial；antifungal
结论摘要：
严重的细菌感染与耐药性已成为全世界迫切的重要课题去开发多靶向抗菌药。该项目参考药物发挥药效作用时利用多种非共价键力与靶分子形成生物超分子的结构特点，开发了一系列喹诺酮唑类新化合物及其类似物，发现了一些新合成反应；一些目标化合物的活性强于临床诺氟沙星和/或氟康唑，体内毒性更低，有适宜的pKa、Log P以及溶解度，无耐药性产生，与临床药物的联用显示更好的疗效；作用机制研究表明，强生物活性分子能形成化合物-Cu2+-DNA三元络合物，呈现多靶向性，可作用于DNA小沟区、嵌入DNA和/或切割 断裂DNA；与人血清蛋白（HSA）的超分子作用研究表明，强活性化合物具有良好的体内存储和运输等能力；尤其是首次用2-氨基噻唑取代抗菌药喹诺酮3-位羧基，开发了一系列氨基噻唑喹诺酮，颠覆了抗菌药喹诺酮的经典结构，有望成为新一代抗菌，这些强活性分子，为解决日趋严重的耐药性提供了希望。 基金资助的相关研究共申请发明专利27件，其中项目执行期间申请发明专利17项，其中4项已授权，前期相关工作申请中国专利10项，其中10项已授权。在该领域顶尖期刊Medicinal Research Reviews等国内外杂志共发表论文43篇，会议论文86篇。其中SCI收录40篇，ESI收录3篇，2014年度中国百篇最具影响国际学术论文1篇，Bentham Science Publisher出版社高引论文奖1篇，《中国科学》杂志优秀论文奖1篇，前期相关工作获“领跑者5000（F5000）—中国精品科技期刊顶尖学术论文”2篇，1篇获提名。主编《基础药物化学》书一部（科学出版社），获邀撰写专著《Advances in Anticancer Agents in Medicinal Chemistry》第二章，正在出版专著《Azole-based Medicinal Chemistry》（Springer出版社）。招收和培养博士后和研究生46人，其中外国留学生10名，包括外国博士后8名，外国博士生2名。组织承办了中国化学会第八届全国有机化学学术会议及首届重庆有机化学国际研讨会，并荣获中国化学会优秀学术交流组织奖，受邀作大会报告3次，邀请报告5次。
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期刊论文
会议论文
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获奖
著作
期刊论文
Synthesis and biological activities of thio-triazole derivatives as novel potential antibacterial an
A series of naphthalimide azoles: design, synthesis and bioactive evaluation as potential antimicrob
Berberine azoles as antimicrobial agents: synthesis, biological evaluation and their interactions wi
A unique one-pot reaction via C-C cleavage from aminomethylene benzimidazoles to access benzimidazol
Design and biological evaluation of novel quinolone-based metronidazole derivatives as potent Cu2+ m
The synthesis and activities of novel mononuclear or dinuclear cyclen complexes bearing azole pendan
Design, synthesis, and biological evaluation of novel benzimidazole derivatives and their interactio
Trifluoroacetic acid–catalyzed synthesis of N-(1-(3-chlorophenyl)-3-aryl-3-oxopropyl)-2-(4-nitrophen
Synthesis and biological evaluation of alpha-triazolyl chalcones as a new type of potential antimicr
Novel berberine triazoles: synthesis, antimicrobial evaluation and competitive interactions with met
Synthesis and bioactive evaluation of novel hybrids of metronidazole and berberine as new type of an
Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DN
Synthesis and biological evaluation of a class of quinolone triazoles as potential antimicrobial age
Synthesis and biological evaluation of schiff base-linked imidazolyl naphthalimides as novel potenti
Coumarin-derived azolyl ethanols: synthesis, antimicrobial evaluation and preliminary action mechani
Synthesis of tetrazole compounds as a novel type of potential antimicrobial agents and their synergi
Novel hybrids of metronidazole and quinolones: synthesis, bioactive evaluation, cytotoxicity, prelim
catena -Poly[[trans -bis(cyclohexane-1,2-diamine-κ2N,N)cadmium]-μ-iodido-(diiodidocadmium)-μ-iodido]
Synthesis and biological evaluation of novel D-glucose-derived 1,2,3-triazoles as potential antibact
Synthesis and biological evaluation of a new class of quinazolinone azoles as potential antimicrobia
Design, synthesis, and antibacterial evaluation of novel azolylthioether quinolones as MRSA DNA inte
Synthesis and bioactive evaluations of novel benzotriazole compounds as potential antimicrobial agen
会议论文
Synthesis and antimicrobial evaluation of novel quinolone imidazoles and their interactions with MRS
Synthesis and their supramolecular transportation and activity of antimicrobial quinazolinone nitroi
Synthesis and relational chemicobiological study of novel antimicrobial naphthalimide-based imidazol
Nitrogen mustard conjugates of naphthalimide-azoles as a new class of antitumor cytostatic agents: d
Novel hybrids of metronidazole and quinolone: synthesis, antimicrobial evaluation and their supramol
Novel hybrids of metronidazole and quinolone: design, synthesis,antimicrobial evaluation and cytotox
Coumarin type of miconazole analogues: biological evaluation and supramolecular intreraction with cy
Synthesis of new quinolones with oxiran-2-ylmethyl moieties at N-1 position and their antifungal act
Synthesis and bioactivity of novel N-alkylated benzimidazole derivatives and interaction with calf t
Synthesis and biological evaluation of novel sulfonylaniline-benzimidazole derivatives as antimicrob
Design and biological evaluation of quinolone-based metronidazole derivative as potent Cu2+ mediated
Synthesis and supramolecular antifungal behavior of novel 1,2,4-triazole quinoline as a new class of
Bis-benzimidazoles: synthesis, antimicrobial activities and supramolecular interaction with bovine s
Coumarin-derived metronidazoles: design, synthesis, activity and supramolecular interaction with DNA
Synthesis of tetrahydroxy bis-benzimidazole and its interaction with muscle relaxation drug macrocyc
A first one-pot reaction via C-C cleavage to access benzimidazolones with wide potential application
A novel reaction of opening ring by C-N breaking to access sulfanilamide triazoles with antimicrobia
Synthesis of selective and high-affinity chalcone-benzothiazole hybrids as brugia malayi thymidylate
Synthesis and biological evaluation of a class of quinolone thiazoleas antimicrobial agents and thei
Synthesis and biological activity of coumarin-metronidazole hybridsas potential antibacterial agents
Novel organophosphorus metronidazoles:synthesis, antimicrobial activity and supramolecular interacti
Synthesis of benzimidazole-based phosphonium salts as novel antimicrobial agents and their bioactivi
A unique C-N breakage of sulfonylated cyclic amines by azole ring toaccess novel antimicrobial sulfo
Synthesis of novel antimicrobial tetrazole compounds and their supramolecular synergistic effects wi
Design and synthesis of novel benzimidazole derivatives and preliminary evaluation for antimicrobial
The effect of metal ions on supramolecular transportation of triazolyl quinolone by human serum albu
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