{"id":2184,"date":"2026-05-07T18:52:38","date_gmt":"2026-05-07T16:52:38","guid":{"rendered":"https:\/\/sites.unica.it\/pe2026\/?p=2184"},"modified":"2026-05-08T17:27:18","modified_gmt":"2026-05-08T15:27:18","slug":"adam-anthony-needle","status":"publish","type":"post","link":"https:\/\/sites.unica.it\/pe2026\/2026\/05\/07\/adam-anthony-needle\/","title":{"rendered":"Adam Anthony Needle"},"content":{"rendered":"\n
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PC25 – Adam Anthony Needle<\/strong><\/p>\n\n\n\n

Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Czech Republic<\/p>\n\n\n\n


ORCID<\/strong>
<\/a>
needlea@faf.cuni.cz<\/strong><\/p>\n<\/div><\/div>\n\n\n\n

Thymosin \u03b24 as a Metal\u2011Responsive Regulator of Ferroptosis and Cellular Stress: Implications for Medicinal Chemistry<\/strong><\/td><\/tr>
Needle Adam A.1<\/sup>, Dole\u017eal Martin1<\/sup>, and Ku\u010derov\u00e1-Chlup\u00e1\u010dov\u00e1 Marta1<\/sup><\/em>

1<\/sup><\/em> Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Akademika Heyrovsk\u00e9ho 1203, 500 03 Hradec Kr\u00e1lov\u00e9, Czech Republic
<\/td><\/tr>
Abstract<\/strong>
Castration resistant prostate cancer, which does not respond to second generation nonsteroidal anti-androgen treatment, is putting pressure on the development of new agents that will antagonise mutant androgen receptor variants and inhibit the binding of male sex hormones [1]. A recent publication by our team has revealed that it is possible to replace the nitro group in the structure of flutamide with a boronic acid functional group [2]. In the structures of second-generation nonsteroidal anti-androgens, the nitrile functional group replaces the original nitro group. We have replaced the nitrile group in enzalutamide analogues with a boronic acid residue that contains two oxygen atoms, which could mimic the nitro group in the flutamide molecule. The initial idea was that boron can form a dative bond with biological nucleophiles in amino acid residues [3]. Preliminary in silico<\/em> studies have shown a hydrogen bond between Met745 and the boronic acid moiety instead of the proposed Arg752. Therefore, non-covalent binding modes may also provide promising molecules. This could lead to the discovery of an agent effective for the treatment of castration-resistant prostate cancer.
The effect of structural modifications on antiandrogenic activity is being studied by introducing various hydrophilic, lipophilic, electron-withdrawing, and electron-donating groups into the structure. Variation of the halogen adjacent to the boronic acid moiety is also examined. Our five-step synthesis process has been successfully optimised and can be utilised in the synthesis of further series. The first series is being evaluated in the LAPC-4 androgen dependent human prostate cancer cell line and in the PC-3 androgen independent human prostate adenocarcinoma cell line. The selectivity of the compounds will be assessed in HepG2 and HK-2 cell lines. To confirm the interaction of the prepared ligands with the androgen receptor, a fluorescence polarisation-based competition binding assay is planned.<\/td><\/tr>
References  <\/strong>
[1] Schmidt, K.; Huitema, A.; et al. Resistance to second-generation androgen receptor antagonists in prostate cancer. Nat. Rev. Urol.<\/em> 2021<\/strong>, 18<\/em>, 209\u2013226. DOI: https:\/\/doi.org\/10.1038\/s41585-021-00438-4
[2] \u0160lechta, P.; Vit\u00e1k, R.; et al. Replacement of nitro function by free boronic acid in non-steroidal anti-androgens. RSC Med. Chem<\/em>. 2024<\/strong>, 15<\/em>(12), 4018\u20134038. DOI: DOI: https:\/\/doi.org\/10.1039\/d4md00343h
[3] Grams, R.; Santos, W.; et al.  The Rise of Boron-Containing Compounds: Advancements in Synthesis, Medicinal Chemistry, and Emerging Pharmacology. Chem. Rev.<\/em> 2024<\/strong>, 124<\/em> (5), 2441-2511. DOI: https:\/\/doi.org\/10.1021\/acs.chemrev.3c00663<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n\n\n\n

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PC25 – Adam Anthony Needle Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Czech Republic ORCIDneedlea@faf.cuni.cz Thymosin \u03b24 as a Metal\u2011Responsive Regulator of Ferroptosis and Cellular Stress: Implications for […]<\/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-2184","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2184","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=2184"}],"version-history":[{"count":2,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2184\/revisions"}],"predecessor-version":[{"id":2349,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2184\/revisions\/2349"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=2184"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=2184"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=2184"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}