[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331343-105":59,"doc-detail-331343-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","privileged-scaffold-hybridization-in-the-design-of-carbonic-anhydrase-inhibitors","Privileged Scaffold Hybridization in the Design of Carbonic Anhydrase Inhibitors","","Human carbonic anhydrases (hCA) participate in cancer development and progression. Isoforms IX and XII are investigated as anticancer targets, with hCA IX overexpressed in hypoxic tumor cells and involved in metabolic reprogramming. To obtain new inhibitors for IX and XII, hybridization of privileged scaffolds—isatins, dihydrothiazoles, and benzenesulfonamides—was used to design isatin thiazolidinone hybrids. Synthesized compounds were evaluated for activity and selectivity against hCA I, II, IX, and XII, showing nanomolar inhibition for IX and XII and highlighting key roles of substituents on the isatin ring and thiazolidinone positions 3 and 5. Molecular docking supported the proposed binding modes of leading compounds, with 5g most active on hCA IX and 5f strongest toward hCA XII.",{"@graph":69,"@context":122},[70,84,105],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/privileged-scaffold-hybridization-in-the-design-of-carbonic-anhydrase-inhibitors/331343/",{"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/privileged-scaffold-hybridization-in-the-design-of-carbonic-anhydrase-inhibitors/331343.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Which carbonic anhydrase isoforms are targeted in the study, and why?","Question",{"text":112,"@type":113},"The study focuses on hCA IX and hCA XII as anticancer targets. hCA IX is overexpressed in hypoxic tumor cells and contributes to metabolic reprogramming.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What scaffold hybridization strategy was used to design the inhibitors?",{"text":117,"@type":113},"Researchers hybridized privileged scaffolds—isatins, dihydrothiazoles, and benzenesulfonamide—to generate isatin thiazolidinone hybrids, then assessed how this affects activity and selectivity.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the key structure–activity insights from the results?",{"text":121,"@type":113},"Compounds showed promising nanomolar inhibitory activity on hCA IX and XII. The results highlight the importance of substituents on the isatin ring and at thiazolidinone positions 3 and 5.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331343,1790942385,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","molecules   \nArticle  \nPrivileged Scaffold Hybridization in the Design of Carbonic Anhydrase Inhibitors  \nDaniela Secci 1, Erica Sanna 1, Simona Distinto 1, Alessia Onali 1, Antonio Lupia 1,2, Laura Demuru 1, Giulia Atzeni 1, Rita Meleddu 1,*, Filippo Cottiglia 1, Andrea Angeli 3, Claudiu T. Supuran 3, *  \nand Elias Maccioni 1  \nCitation: Secci, D.; Sanna, E.; Distinto, S.; Onali, A.; Lupia, A.; Demuru, L.; Atzeni, G.; Meleddu, R.; Cottiglia, F.; Angeli, A.; et al. Privileged Scaffold Hybridization in the Design of Carbonic Anhydrase Inhibitors. Molecules 2024, 29, 4444 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules29184444  \nAcademic Editor: Florenci  \nV. González  \nReceived: 31 July 2024  \nRevised: 2 September 2024  \nAccepted: 12 September 2024  \nPublished: 19 September 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, Italy; [daniela.secci@ffa.uni-lj.si](daniela.secci@ffa.uni-lj.si) (D.S.); [erica.sanna@unica.it](erica.sanna@unica.it) (E.S.); [s.distinto@unica.it](s.distinto@unica.it) (S.D.); [alessia.onali@unica.it](alessia.onali@unica.it) (A.O.); [antonio.lupia@unica.it](antonio.lupia@unica.it) (A.L.); [laura.demuru2@unica.it](laura.demuru2@unica.it) (L.D.); [giulia.atzeni@unica.it](giulia.atzeni@unica.it) (G.A.); [filippo.cottiglia@unica.it](filippo.cottiglia@unica.it) (F.C.); [elias.maccioni@unica.it](elias.maccioni@unica.it) (E.M.)  \n2 Net4Science S.r.l, Università Degli Studi “Magna Græcia” di Catanzaro, 88100 Catanzaro, Italy  \n3 Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Università degli Studi di Firenze, Sesto Fiorentino, 50019 Florence, Italy; [andrea.angeli@unifi.it](andrea.angeli@unifi.it)  \n* Correspondence: rita.meleddu@unica.it (R.M.); [claudiu.supuran@unifi.it](claudiu.supuran@unifi.it) (C.T.S.)  \nAbstract: Human Carbonic Anhydrases (hCA) are enzymes that contribute to cancer’s development and progression. Isoforms IX and XII have been identified as potential anticancer targets, and, more specifically, hCA IX is overexpressed in hypoxic tumor cells, where it plays an important role in reprogramming the metabolism. With the aim to find new inhibitors towards IX and XII isoforms, the hybridization of the privileged scaffolds isatin, dihydrothiazole, and benzenesulfonamide was investigated in order to explore how it may affect the activity and selectivity of the hCA isoforms. In this respect, a series of isatin thiazolidinone hybrids have been designed and synthesized and their biological activity and selectivity on hCA I, hCA II, hCA IX, and hCA XII explored. The new compounds exhibited promising inhibitory activity results on isoforms IX and XII in the nanomolar range, which has highlighted the importance of substituents in the isatin ring and in position 3 and 5 of thiazolidinone. In particular, compound 5g was the most active toward hCA IX, while 5f was the most potent inhibitor of hCA XII within the series. When both potency and selectivity were considered, compound 5f appeared as one of the most promising. Additionally, our investigations were supported by molecular docking experiments, which have highlighted the putative binding poses of the most promising compound.  \nKeywords: carbonic anhydrases inhibitors; scaffold hybridization; benzenesulfonamide-based zinc binders  \n1. Introduction  \nCancer is a complex disease, where multiple implicated genes may simultaneously display mutations that interfere with the physiological processes of cells and cause a rise in malignant phenotype [1,2] . There","cbCaiiCBxjaTMFOZ","https://ap.wps.com/l/cbCaiiCBxjaTMFOZ","pdf",7725509,16,"English","# Introduction\n## Background on carbonic anhydrases in cancer\n## Targeting hCA IX and hCA XII with inhibitors\n# Abstract","[{\"question\":\"Which carbonic anhydrase isoforms are targeted in the study, and why?\",\"answer\":\"The study focuses on hCA IX and hCA XII as anticancer targets. hCA IX is overexpressed in hypoxic tumor cells and contributes to metabolic reprogramming.\"},{\"question\":\"What scaffold hybridization strategy was used to design the inhibitors?\",\"answer\":\"Researchers hybridized privileged scaffolds—isatins, dihydrothiazoles, and benzenesulfonamide—to generate isatin thiazolidinone hybrids, then assessed how this affects activity and selectivity.\"},{\"question\":\"What were the key structure–activity insights from the results?\",\"answer\":\"Compounds showed promising nanomolar inhibitory activity on hCA IX and XII. The results highlight the importance of substituents on the isatin ring and at thiazolidinone positions 3 and 5.\"}]","Privileged Scaffold Hybridization in the Design of Carbonic Anhydrase Inhibitors | PDF",1789992748]