{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T07:18:40Z","timestamp":1771658320569,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Partenariat Hubert Curien-Utique (PHC-Utique)","award":["[code 17G 0811]"],"award-info":[{"award-number":["[code 17G 0811]"]}]},{"name":"Tunisian Ministry of Higher Education and Scientific Research","award":["(LR20IPT01)"],"award-info":[{"award-number":["(LR20IPT01)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Glioblastoma is the most aggressive and invasive form of central nervous system tumors due to the complexity of the intracellular mechanisms and molecular alterations involved in its progression. Unfortunately, current therapies are unable to stop its neoplastic development. In this context, we previously identified and characterized AaTs-1, a tetrapeptide (IWKS) from Androctonus autralis scorpion venom, which displayed an anti-proliferative effect against U87 cells with an IC50 value of 0.57 mM. This peptide affects the MAPK pathway, enhancing the expression of p53 and altering the cytosolic calcium concentration balance, likely via FPRL-1 receptor modulation. In this work, we designed and synthesized new dendrimers multi-branched molecules based on the sequence of AaTs-1 and showed that the di-branched (AaTs-1-2B), tetra-branched (AaTs-1-4B) and octo-branched (AaTs-1-8B) dendrimers displayed 10- to 25-fold higher effects on the proliferation of U87 cells than AaTs-1. We also found that the effects of the newly designed molecules are mediated by the enhancement of the ERK1\/2 and AKT phosphorylated forms and by the increase in p53 expression. Unlike AaTs-1, AaTs-1-8B and especially AaTs-1-4B affected the migration of the U87 cells. Thus, the multi-branched peptide synthesis strategy allowed us to make molecules more active than the linear peptide against the proliferation of U87 glioblastoma cells.<\/jats:p>","DOI":"10.3390\/molecules27030806","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T04:49:51Z","timestamp":1643258991000},"page":"806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Strengthening Anti-Glioblastoma Effect by Multi-Branched Dendrimers Design of a Scorpion Venom Tetrapeptide"],"prefix":"10.3390","volume":"27","author":[{"given":"Wassim","family":"Moslah","sequence":"first","affiliation":[{"name":"Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), LR20IPT01, Institut Pasteur de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1002, Tunisia"},{"name":"Institut de Neurophysiopathologie (INP), UMR 7051-CNRS, Facult\u00e9 de M\u00e9decine, Aix-Marseille Universit\u00e9, 27 bd Jean Moulin, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8049-8950","authenticated-orcid":false,"given":"Dorra","family":"Aissaoui-Zid","sequence":"additional","affiliation":[{"name":"Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), LR20IPT01, Institut Pasteur de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soioulata","family":"Aboudou","sequence":"additional","affiliation":[{"name":"Institut de Chimie Radicalaire (ICR), Aix-Marseille Universit\u00e9, CNRS, ICR UMR 7273, 13397 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaineb","family":"Abdelkafi-Koubaa","sequence":"additional","affiliation":[{"name":"Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), LR20IPT01, Institut Pasteur de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-3397","authenticated-orcid":false,"given":"Marie","family":"Potier-Cartereau","sequence":"additional","affiliation":[{"name":"N2C UMR 1069, INSERM, Facult\u00e9 des Sciences et Techniques, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aude","family":"Lemettre","sequence":"additional","affiliation":[{"name":"N2C UMR 1069, INSERM, Facult\u00e9 des Sciences et Techniques, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2224-0211","authenticated-orcid":false,"given":"Ines","family":"ELBini-Dhouib","sequence":"additional","affiliation":[{"name":"Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), LR20IPT01, Institut Pasteur de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naziha","family":"Marrakchi","sequence":"additional","affiliation":[{"name":"Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), LR20IPT01, Institut Pasteur de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Gigmes","sequence":"additional","affiliation":[{"name":"Institut de Chimie Radicalaire (ICR), Aix-Marseille Universit\u00e9, CNRS, ICR UMR 7273, 13397 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Vandier","sequence":"additional","affiliation":[{"name":"N2C UMR 1069, INSERM, Facult\u00e9 des Sciences et Techniques, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7419-6016","authenticated-orcid":false,"given":"Jos\u00e9","family":"Luis","sequence":"additional","affiliation":[{"name":"Institut de Neurophysiopathologie (INP), UMR 7051-CNRS, Facult\u00e9 de M\u00e9decine, Aix-Marseille Universit\u00e9, 27 bd Jean Moulin, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamel","family":"Mabrouk","sequence":"additional","affiliation":[{"name":"Institut de Chimie Radicalaire (ICR), Aix-Marseille Universit\u00e9, CNRS, ICR UMR 7273, 13397 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najet","family":"Srairi-Abid","sequence":"additional","affiliation":[{"name":"Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), LR20IPT01, Institut Pasteur de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pharmthera.2015.05.005","article-title":"Glioblastoma Multiforme: Pathogenesis and Treatment","volume":"152","author":"Alifieris","year":"2015","journal-title":"Pharmacol. 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