![\"\"](\"http:\/\/sites.unica.it\/pe2026\/files\/2025\/09\/cropped-00_Profile_Tondo-Social__Spilla_PE26_1200px.png\")
<\/figure>PC1 – Francesca Arrighi<\/strong><\/p>\n\n\n\n Department of Drug Chemistry and Technologies, Sapienza University of Rome, Italy<\/p>\n\n\n\n francesca.arrighi@uniroma1.it<\/strong><\/p>\n<\/div><\/div>\n\n\n\n PC1 – Francesca Arrighi Department of Drug Chemistry and Technologies, Sapienza University of Rome, Italy francesca.arrighi@uniroma1.it From Small Molecules to Big Outcomes: Advancing Benzo[b]thiophenes in Neurodegeneration Francesca Arrighi a,1,Emanuela Berrino a,b,1, Paolo Guglielmi a,*, Simone Carradori […]<\/p>\n","protected":false},"author":10371,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-2010","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2010","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/users\/10371"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=2010"}],"version-history":[{"count":3,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2010\/revisions"}],"predecessor-version":[{"id":2305,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2010\/revisions\/2305"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=2010"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=2010"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=2010"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}From Small Molecules to Big Outcomes: Advancing Benzo[b]thiophenes in Neurodegeneration<\/strong><\/td><\/tr> Francesca Arrighi a,1<\/sup><\/em>,Emanuela Berrino a,b,1<\/sup>, Paolo Guglielmi a,*<\/sup>, Simone Carradori c,*<\/sup>, Guya Diletta Marconi d<\/sup>, Jacopo Pizzicannella d<\/sup>, Simone Guarnieri e<\/sup>, Tiziano Tuccinardi f<\/sup>, Giulio Poli f<\/sup>, Federico Pepi a<\/sup>, Anna Troiani a<\/sup>, Chiara Salvitti a<\/sup>, Alessia Di Noi a<\/sup>, Michele Coluccia a<\/sup>, Giorgio Buttitta a<\/sup>, Virginia Pontecorvi a,g<\/sup>, Arianna Granese a<\/sup>, Paola Chimenti a<\/sup>, Daniela Secci a<\/sup>, Anel Petzer h,i<\/sup>, Jacobus Petzer h,i<\/sup>, Francesca Diomede d<\/sup><\/em>
a<\/sup> <\/em>Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
b <\/sup><\/em>Department of Life Science, Health, and Health Professions, Link Campus University, Via del Casale di San Pio V, 44 \u2013 00165, Rome, Italy
c <\/sup><\/em>Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
d <\/sup><\/em>Department of Innovative Technologies in Medicine & Dentistry, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, Chieti, Italy
e<\/sup> <\/em>Department of Neuroscience, Imaging and Clinical Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, Via Luigi Polacchi 11, 66100 Chieti, Italy
f <\/sup><\/em>Department of Pharmacy, Universit\u00e0 di Pisa, via Bonanno 6, 56126 Pisa, Italy
g<\/sup> <\/em>Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100, Latina, Italy
h <\/sup>Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, 2520, South Africa
i <\/sup><\/em>Pharmaceutical Chemistry, School of Pharmacy and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, <\/em>South Africa<\/td><\/tr>Abstract<\/strong>
Neurodegenerative disorders represent an increasing burden in ageing societies. In Parkinson\u2019s disease, the elevated activity of hMAO-B contributes to oxidative stress and dopaminergic neurodegeneration, supporting selective hMAO-B inhibition as a valuable therapeutic strategy. Building on previous studies on benzofuran and benzothiophene-3-ol scaffolds, this work explores 2-aroylbenzothiophene derivatives as novel candidates for neurodegeneration-oriented drug discovery (Figure 1). Screening against hMAO-A and hMAO-B identified compounds 4, 11, and 12 as the most promising inhibitors. These derivatives were further evaluated in preliminary cellular assays: while compound 4 showed significant cytotoxicity, associated with increased ROS production and potential mitochondrial liability, compounds 11 and 12 were well tolerated up to 100 \u03bcM, displaying a safety profile comparable to (R<\/em>)-(-)-Deprenyl. Notably, compound 12 exhibited antioxidant-like properties, significantly reducing basal ROS levels and showing modest neuroprotective effects after 24 h in SH-SY5Y cells exposed to 6-OHDA. Molecular modelling studies further supported the proposed binding modes. Overall, a novel class of 2-aroylbenzothiophenes has been identified as selective, nanomolar hMAO-B inhibitors, with activity finely modulated by aryl substitution \u00b9.<\/td><\/tr>References <\/strong>
[1] Guglielmi, P. et al. Benzo[b]thiophen-3-ol derivatives as effective inhibitors of human monoamine oxidase: design, synthesis, and biological activity. J Enzyme Inhib Med Chem 34, 1511\u20131525 (2019)
[2] Arrighi, F et al. Novel Insights on Benzo[b<\/em>]thiophene Analogues for MAO-B Inhibition and Neuroprotection: Design, Synthesis, Molecular Modelling Studies and Biological Activity. Antioxidants<\/em> 2026<\/strong>, 15<\/em>, 346. https:\/\/doi.org\/10.3390\/antiox15030346<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n","protected":false},"excerpt":{"rendered":"