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It explains how secondary metabolites historically guided medicine development, while HTS accelerates hit identification but demands substantial initial investment. Despite combinatorial chemistry integration, natural products remain key starting materials, supported by reported anticancer entity statistics. Research at the Department of Pharmacy in Naples focuses on isolation and characterization of secondary metabolites, and design, synthesis, and evaluation of bile acid receptor dual agonists.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/from-natural-products-chemistry-to-hts-by-nmr-different-approaches-in-drug-discovery-phd-thesis/199483/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/from-natural-products-chemistry-to-hts-by-nmr-different-approaches-in-drug-discovery-phd-thesis/199483.png","ImageObject",300,407,{"name":92,"@type":93},"Genevieve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-17","2026-09-04",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",15,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What main research strategies does the thesis compare for drug discovery?","Question",{"text":113,"@type":114},"It compares natural products chemistry with high-throughput screening (HTS) by NMR, emphasizing how different approaches converge on identifying and optimizing pharmacologically active molecules.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What is investigated regarding marine natural products in Chapter 1?",{"text":118,"@type":114},"The thesis isolates and structurally characterizes marine naturally occurring compounds from Sinularia inelegans, including the novel norcembranoid 5-epinorcembrenolide, using high-resolution mass spectrometry and 1D/2D NMR.",{"name":120,"@type":111,"acceptedAnswer":121},"What work is carried out on bile acid receptors?",{"text":122,"@type":114},"The thesis covers the design, synthesis, and pharmacological evaluation of bile acid receptor dual agonists, including pharmacological evaluation and docking studies.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},199483,1788506110,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":130,"read_time":145,"preview_page_count":4},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","UNIVERSITY OF NAPLES FEDERICO II  \nPHARMACY DEPARTMENT  \nPh.D. programme in  \nPHARMACEUTICAL SCIENCE  \nXXVII CYCLE (2012-2015)  \nFrom natural products chemistry to HTS by NMR: different approaches in drug discovery  \nPh.D. Chiara Del Gaudio  \nTutors:  \nProf. F. Zollo  \n(University Federico II)  \nCoordinator:  \nProf. M.V. D’Auria  \nProf. M. Pellecchia  \n(Sanford-Burnham MRI)  \nGive the ones you love wings to fly,  \nroots to come back, reasons to stay.  \nIndex  \nINDEX  \nABSTRACT…………………………………………………………………..1  \nINTRODUCTION…………………………………………………………...4  \nCHAPTER 1………………………………………………………………….8  \nISOLATION AND STRUCTURAL CHARACTERIZATION OF MARINE NATURALLY-OCCURRING COMPOUNDS 1.1 Research steps………………………………………………………………..10  \n1.1.1 Isolation and purification procedures…………………………………...10  \n1.1.2 Structural characterization methods…………………………………….12  \n1.1.2.1 Stereochemistry determination…………………...……………...........14  \n1.2 Sinularia inelegans…………………………………………………………...16  \n1.2.1 Isolation and structural characterization of norcembranoids…………...18  \n1.2.2 Structural determination of 5-epi-norcembrenolide…………………….20  \n1.2.3 Conclusions…………………………………………………………......24  \nCHAPTER 2………………………………………………………………..26  \nDESIGN, SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIP OF BILE ACIDS DERIVATIVES. 2.1 Dual agonists of nuclear and membrane bile acid receptors…………………27  \n2.2 Total synthesis of INT-767…………………………………………………..28  \n2.3 Total synthesis of INT-767 derivatives………………………………………31  \n2.3.1 Chenodeoxycholan sulfate derivatives………………………………….31  \n2.3.2 Ursodeoxycholan sulfate derivatives…………………………………....32  \n2.4 Pharmacological evaluation……………………………………………….....33  \n2.5 Docking studies……………………………………………………………....38  \n2.6 Conclusions………………………………………………………………......44  \nCHAPTER 3........................................................................................46  \nIndex  \nFRAGMENT-INSPIRED HTS BY NMR OF COMBINATORIAL LIBRARIES: APPLICATION TO ANTAGONISTS OF PROTEIN  \nPROTEIN INTERACTIONS 3.1 Design and optimization of potent inhibitors of XIAP, a member of the Inhibitor of Apoptosis Proteins family..............................................................50  \n3.1.1 Library, screening and results...................................................................52  \n3.1.2 Lead optimization.....................................................................................55  \n3.1.3 Computational studies .............................................................................58  \n3.1.4 Conclusions..............................................................................................59  \n3.2 Discovery and optimization of hit compounds binding EphA3, a tyrosine kinase receptor involved in angiogenesis and metastasis formation...............60  \n3.2.1 EphA3-LBD expression ..........................................................................62  \n3.2.2 Binders design and optimization .............................................................63  \n3.2.3 Conclusions..............................................................................................66  \nEXPERIMENTAL SECTION  \nI. Experimental procedures for Sinularia inelegans..........................................68  \nII. Experimental procedures for FXR/GP-BAR1 dual agonists.......................79  \nIII. Experimental procedures for XIAP-BIR3 inhibitors................................107  \nIV. Experimental procedures for EphA3 inhibitors........................................112  \nREFERENCES................................................................................. 114  \nAbstract  \nABSTRACT  \nThe process of drug discovery, by which new potential medicines are discovered, is a long and intricate path that can be approached with many different strategies. For a long time, drugs have been discovered by studying secondary metabolites produced by plants and other organisms mainly as defense or as a way to interact with competitors and mutualists. During recent years, high-throughpu","cbCaiow9zpDFdpm2","https://ap.wps.com/l/cbCaiow9zpDFdpm2","pdf",18876753,132,"English","# Abstract\n# Introduction\n# Chapter 1\n## Isolation and Structural Characterization of Marine Naturally-Occurring Compounds\n# Chapter 2\n## Design, Synthesis and Structure-Activity Relationship of Bile Acids Derivatives\n# Chapter 3\n## Fragment-Inspired HTS by NMR of Combinatorial Libraries","[{\"question\":\"What main research strategies does the thesis compare for drug discovery?\",\"answer\":\"It compares natural products chemistry with high-throughput screening (HTS) by NMR, emphasizing how different approaches converge on identifying and optimizing pharmacologically active molecules.\"},{\"question\":\"What is investigated regarding marine natural products in Chapter 1?\",\"answer\":\"The thesis isolates and structurally characterizes marine naturally occurring compounds from Sinularia inelegans, including the novel norcembranoid 5-epinorcembrenolide, using high-resolution mass spectrometry and 1D/2D NMR.\"},{\"question\":\"What work is carried out on bile acid receptors?\",\"answer\":\"The thesis covers the design, synthesis, and pharmacological evaluation of bile acid receptor dual agonists, including pharmacological evaluation and docking studies.\"}]","From natural products chemistry to HTS by NMR: different approaches in drug discovery - Ph.D. Thesis | PDF",333]