{"id":21508,"date":"2025-02-17T17:40:47","date_gmt":"2025-02-17T16:40:47","guid":{"rendered":"https:\/\/sano.science\/?post_type=research&#038;p=21508"},"modified":"2025-02-17T17:51:45","modified_gmt":"2025-02-17T16:51:45","slug":"multifunctional-fluorene-based-modulator-of-cholinergic-and-gabaergic-neurotransmission-as-a-novel-drug-candidate-for-palliative-treatment-of-alzheimers-disease","status":"publish","type":"research","link":"https:\/\/sano.science\/research\/multifunctional-fluorene-based-modulator-of-cholinergic-and-gabaergic-neurotransmission-as-a-novel-drug-candidate-for-palliative-treatment-of-alzheimers-disease\/","title":{"rendered":"Multifunctional, Fluorene-Based Modulator of Cholinergic and GABAergic Neurotransmission as a Novel Drug Candidate for Palliative Treatment of Alzheimer&#8217;s Disease"},"content":{"rendered":"\n<p class=\" eplus-wrapper\">Dr. Dawid Panek,&nbsp;Dr. Anna Pasieka,&nbsp;Dr. <a href=\"https:\/\/sano.science\/people\/jakub-jonczyk\/\">Jakub Jo\u0144czyk<\/a>,&nbsp;Milena Gawli\u0144ska,&nbsp;Dr. Paula Zar\u0119ba,&nbsp;Dr. Agata Siwek,&nbsp;Dr. Ma\u0142gorzata Wolak,&nbsp;Dr. Barbara Mordyl,&nbsp;Dr. Monika G\u0142uch-Lutwin,&nbsp;Dr. Gniewomir Latacz,&nbsp;Dr. Xavier Brazzolotto,&nbsp;Dr. Fabien Chantegreil,&nbsp;Dr. Florian Nachon,&nbsp;Prof.\u2005Dr. Jana Zdarova Karasova,&nbsp;Dr. Jaroslav Pejchal,&nbsp;Dr. Martin Mzik,&nbsp;Dr. Vit Sestak,&nbsp;Lukas Prchal,&nbsp;Dr. Jitka Odvarkova,&nbsp;Dr. Ondrej Soukup,&nbsp;Prof.\u2005Dr. Jan Korabecny,&nbsp;Dr. Ales Sorf,&nbsp;Dr. Marie Hamsikova,&nbsp;Dr. Lucie Zemanova,&nbsp;Dr. Lubica Muckova,&nbsp;Dr. Nela V\u00e1nova,&nbsp;Pola Dryja,&nbsp;Prof.\u2005Dr. Kinga Sa\u0142at,&nbsp;Dr. Georg H\u00f6fner,&nbsp;Prof.\u2005Dr. Klaus Wanner,&nbsp;Dr. Anna Wi\u0119ckowska,&nbsp;Prof.\u2005Dr. Barbara Malawska<\/p>\n\n\n\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n\n\n\n<p class=\" eplus-wrapper\">Progressive cognitive decline characterizing Alzheimer&#8217;s disease (AD) includes memory impairments and various behavioral and psychological symptoms of dementia (BPSD). Treatments traditionally target the predominantly affected cholinergic neurons to boost neurotransmission. However, dysfunctions in additional neurotransmitters such as \u03b3-aminobutyric acid (GABA) also significantly influence AD\u2019s clinical manifestations. This research introduces compound 6, developed through a blend of crystallography and computational analytics, serving as a dual regulator of GABAergic and cholinergic transmission. It effectively inhibits BuChE (IC50=0.21\u2005\u03bcM) and GABA transporters 1 (IC50=10.96\u2005\u03bcM) and 3 (IC50=7.76\u2005\u03bcM), with a robust profile suitable for drug development. Compound 6&#8217;s efficacy in improving memory retention and mitigating symptoms of anxiety and depression was confirmed through in vivo tests, showing it to be safe and orally bioavailable. Offering a novel, multi-targeted therapeutic strategy, compound 6 holds potential for managing cognitive deficits and BPSD in Alzheimer\u2019s disease.<\/p>\n\n\n\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n\n\n\n<p class=\" eplus-wrapper\"><strong>DOI<\/strong>: 10.1002\/anie.202420510<\/p>\n\n\n\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n\n\n\n\t\n    \n        \n\t\t\t<a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202420510\" target=\"_self\"  class=\"button primary \">\n\n\t\t\t\t<span>\n\t\t\t\t\tREAD HERE\n\t\t\t\t<\/span>\n\n\t\t\t<\/a>\n\n        \n    \n","protected":false},"excerpt":{"rendered":"<p>In: Angewandte Chemie International Edition, 2024<\/p>\n","protected":false},"featured_media":0,"template":"","research_type":[8],"research_team":[],"class_list":["post-21508","research","type-research","status-publish","hentry","research_type-publications"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.3 (Yoast SEO v27.3) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Multifunctional, Fluorene-Based Modulator of Cholinergic and GABAergic Neurotransmission as a Novel Drug Candidate for Palliative Treatment of Alzheimer&#039;s Disease - Centre for Computational Personalized Medicine<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/sano.science\/research\/multifunctional-fluorene-based-modulator-of-cholinergic-and-gabaergic-neurotransmission-as-a-novel-drug-candidate-for-palliative-treatment-of-alzheimers-disease\/\" \/>\n<meta property=\"og:locale\" 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Chantegreil,&nbsp;Dr. Florian Nachon,&nbsp;Prof.\u2005Dr. Jana Zdarova Karasova,&nbsp;Dr. Jaroslav Pejchal,&nbsp;Dr. Martin Mzik,&nbsp;Dr. Vit Sestak,&nbsp;Lukas Prchal,&nbsp;Dr. Jitka Odvarkova,&nbsp;Dr. Ondrej Soukup,&nbsp;Prof.\u2005Dr. Jan Korabecny,&nbsp;Dr. Ales Sorf,&nbsp;Dr. Marie Hamsikova,&nbsp;Dr. Lucie Zemanova,&nbsp;Dr. Lubica Muckova,&nbsp;Dr. Nela V\u00e1nova,&nbsp;Pola Dryja,&nbsp;Prof.\u2005Dr. Kinga Sa\u0142at,&nbsp;Dr. Georg H\u00f6fner,&nbsp;Prof.\u2005Dr. Klaus Wanner,&nbsp;Dr. Anna Wi\u0119ckowska,&nbsp;Prof.\u2005Dr. Barbara Malawska<\/p>\n","innerContent":["\n<p class=\" eplus-wrapper\">Dr. Dawid Panek,&nbsp;Dr. Anna Pasieka,&nbsp;Dr. <a href=\"https:\/\/sano.science\/people\/jakub-jonczyk\/\">Jakub Jo\u0144czyk<\/a>,&nbsp;Milena Gawli\u0144ska,&nbsp;Dr. Paula Zar\u0119ba,&nbsp;Dr. Agata Siwek,&nbsp;Dr. Ma\u0142gorzata Wolak,&nbsp;Dr. Barbara Mordyl,&nbsp;Dr. Monika G\u0142uch-Lutwin,&nbsp;Dr. Gniewomir Latacz,&nbsp;Dr. Xavier Brazzolotto,&nbsp;Dr. Fabien Chantegreil,&nbsp;Dr. Florian Nachon,&nbsp;Prof.\u2005Dr. Jana Zdarova Karasova,&nbsp;Dr. Jaroslav Pejchal,&nbsp;Dr. Martin Mzik,&nbsp;Dr. Vit Sestak,&nbsp;Lukas Prchal,&nbsp;Dr. Jitka Odvarkova,&nbsp;Dr. Ondrej Soukup,&nbsp;Prof.\u2005Dr. Jan Korabecny,&nbsp;Dr. Ales Sorf,&nbsp;Dr. Marie Hamsikova,&nbsp;Dr. Lucie Zemanova,&nbsp;Dr. Lubica Muckova,&nbsp;Dr. Nela V\u00e1nova,&nbsp;Pola Dryja,&nbsp;Prof.\u2005Dr. Kinga Sa\u0142at,&nbsp;Dr. Georg H\u00f6fner,&nbsp;Prof.\u2005Dr. Klaus Wanner,&nbsp;Dr. Anna Wi\u0119ckowska,&nbsp;Prof.\u2005Dr. Barbara Malawska<\/p>\n"]},{"blockName":"core\/spacer","attrs":{"height":"30px","epAnimationGeneratedClass":"edplus_anim-V2l7ci","epGeneratedClass":"eplus-wrapper"},"innerBlocks":[],"innerHTML":"\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n","innerContent":["\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n"]},{"blockName":"core\/paragraph","attrs":{"epAnimationGeneratedClass":"edplus_anim-7dFj5s","epGeneratedClass":"eplus-wrapper"},"innerBlocks":[],"innerHTML":"\n<p class=\" eplus-wrapper\">Progressive cognitive decline characterizing Alzheimer's disease (AD) includes memory impairments and various behavioral and psychological symptoms of dementia (BPSD). Treatments traditionally target the predominantly affected cholinergic neurons to boost neurotransmission. However, dysfunctions in additional neurotransmitters such as \u03b3-aminobutyric acid (GABA) also significantly influence AD\u2019s clinical manifestations. This research introduces compound 6, developed through a blend of crystallography and computational analytics, serving as a dual regulator of GABAergic and cholinergic transmission. It effectively inhibits BuChE (IC50=0.21\u2005\u03bcM) and GABA transporters 1 (IC50=10.96\u2005\u03bcM) and 3 (IC50=7.76\u2005\u03bcM), with a robust profile suitable for drug development. Compound 6's efficacy in improving memory retention and mitigating symptoms of anxiety and depression was confirmed through in vivo tests, showing it to be safe and orally bioavailable. Offering a novel, multi-targeted therapeutic strategy, compound 6 holds potential for managing cognitive deficits and BPSD in Alzheimer\u2019s disease.<\/p>\n","innerContent":["\n<p class=\" eplus-wrapper\">Progressive cognitive decline characterizing Alzheimer's disease (AD) includes memory impairments and various behavioral and psychological symptoms of dementia (BPSD). Treatments traditionally target the predominantly affected cholinergic neurons to boost neurotransmission. However, dysfunctions in additional neurotransmitters such as \u03b3-aminobutyric acid (GABA) also significantly influence AD\u2019s clinical manifestations. This research introduces compound 6, developed through a blend of crystallography and computational analytics, serving as a dual regulator of GABAergic and cholinergic transmission. It effectively inhibits BuChE (IC50=0.21\u2005\u03bcM) and GABA transporters 1 (IC50=10.96\u2005\u03bcM) and 3 (IC50=7.76\u2005\u03bcM), with a robust profile suitable for drug development. Compound 6's efficacy in improving memory retention and mitigating symptoms of anxiety and depression was confirmed through in vivo tests, showing it to be safe and orally bioavailable. Offering a novel, multi-targeted therapeutic strategy, compound 6 holds potential for managing cognitive deficits and BPSD in Alzheimer\u2019s disease.<\/p>\n"]},{"blockName":"core\/spacer","attrs":{"height":"30px","epAnimationGeneratedClass":"edplus_anim-V2l7ci","epGeneratedClass":"eplus-wrapper"},"innerBlocks":[],"innerHTML":"\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n","innerContent":["\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n"]},{"blockName":"core\/paragraph","attrs":{"epAnimationGeneratedClass":"edplus_anim-p5dL3M","epGeneratedClass":"eplus-wrapper"},"innerBlocks":[],"innerHTML":"\n<p class=\" eplus-wrapper\"><strong>DOI<\/strong>: 10.1002\/anie.202420510<\/p>\n","innerContent":["\n<p class=\" eplus-wrapper\"><strong>DOI<\/strong>: 10.1002\/anie.202420510<\/p>\n"]},{"blockName":"core\/spacer","attrs":{"height":"30px","epAnimationGeneratedClass":"edplus_anim-V2l7ci","epGeneratedClass":"eplus-wrapper"},"innerBlocks":[],"innerHTML":"\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n","innerContent":["\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n"]},{"blockName":"acf\/button","attrs":{"title":"READ HERE","button_type":"link","url":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202420510","button_style":"primary","target":"_self","button_extra_classes":""},"innerBlocks":[],"innerHTML":"","innerContent":[]}],"meta_data":{"is_automatically_other_posts":true,"number_of_posts":"3","is_automatically_check_also_posts":true},"_links":{"self":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research\/21508","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research"}],"about":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/types\/research"}],"version-history":[{"count":14,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research\/21508\/revisions"}],"predecessor-version":[{"id":21522,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research\/21508\/revisions\/21522"}],"wp:attachment":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/media?parent=21508"}],"wp:term":[{"taxonomy":"research_type","embeddable":true,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research_type?post=21508"},{"taxonomy":"research_team","embeddable":true,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research_team?post=21508"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}