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G\u2010quadruplexes (G4), Guanine\u2010rich secondary structures of DNA and RNA sequences, have an essential role in cell survival and cell metabolism regulation, including in\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    . We have recently demonstrated that the G\u2010quadruplex ligand RHPS4, an acridine derivative, displays strong antiplasmodial activity by disrupting\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    through G4 stabilization, leading to parasite death. Based on this original mode of action, we propose here a series of new RHPS4 analogues. These derivatives were then tested against\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    and on human cells to evaluate their selectivity index. They exhibited IC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 70\u2009nM to up to 10\u2009\u00b5M with cationic analogues more active than neutral ones. Their ability to interact and stabilize G\u2010quadruplex DNA structures was also evaluated. Among all RHPS4 analogues, the compound\n                    <jats:bold>8b<\/jats:bold>\n                    (N8\u2010ethyl) exhibited the best activity (70\u2009nM), a high selectivity index (143), and a significant capacity to stabilize the G4 structures.\n                  <\/jats:p>","DOI":"10.1002\/cbic.70516","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:11:57Z","timestamp":1789103517000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["N8\u2010Modified Quino[4,3,2\u2010\n                    <i>kl<\/i>\n                    ]acridines as Promising Antimalarial G\u2010Quadruplex Ligands"],"prefix":"10.1002","volume":"27","author":[{"given":"Steve","family":"Saulnier","sequence":"first","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS (LCC\u2010CNRS) Inserm ERL 1289 MAAP Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Ant\u00f4nio G. B.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS (LCC\u2010CNRS) Inserm ERL 1289 MAAP Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Salim","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS (LCC\u2010CNRS) Inserm ERL 1289 MAAP Universit\u00e9 de Toulouse  Toulouse France"},{"name":"Institut de Pharmacologie et de Biologie Structurale (IPBS) Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7340-0517","authenticated-orcid":false,"given":"Maxime","family":"Guichonnet","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS (LCC\u2010CNRS) Inserm ERL 1289 MAAP Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6496-0495","authenticated-orcid":false,"given":"Michel","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS (LCC\u2010CNRS) Inserm ERL 1289 MAAP Universit\u00e9 de Toulouse  Toulouse France"},{"name":"Institut de Pharmacologie et de Biologie Structurale (IPBS) Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7111-9258","authenticated-orcid":false,"given":"Laure","family":"Vendier","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS (LCC\u2010CNRS) Inserm ERL 1289 MAAP Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3811-1633","authenticated-orcid":false,"given":"Flore","family":"Nardella","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS (LCC\u2010CNRS) Inserm ERL 1289 MAAP Universit\u00e9 de Toulouse  Toulouse France"},{"name":"Institut de Pharmacologie et de Biologie Structurale (IPBS) Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2847-1969","authenticated-orcid":false,"given":"Jean\u2010Michel","family":"Augereau","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS (LCC\u2010CNRS) Inserm ERL 1289 MAAP Universit\u00e9 de Toulouse  Toulouse France"},{"name":"Institut de Pharmacologie et de Biologie Structurale (IPBS) Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9942-1451","authenticated-orcid":false,"given":"Dennis","family":"Gomez","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et de Biologie Structurale (IPBS) Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9092-6776","authenticated-orcid":false,"given":"Anne","family":"Robert","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS (LCC\u2010CNRS) Inserm ERL 1289 MAAP Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9468-4823","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Benoit\u2010Vical","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS (LCC\u2010CNRS) Inserm ERL 1289 MAAP Universit\u00e9 de Toulouse  Toulouse France"},{"name":"Institut de Pharmacologie et de Biologie Structurale (IPBS) Universit\u00e9 de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"WHO Malaria Report 2025; World Health Organization accessed 2025 https:\/\/www.who.int\/teams\/global\u2010malaria\u2010programme\/reports\/world\u2010malaria\u2010report\u20102025."},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0805011"},{"key":"e_1_2_13_5_1","unstructured":"WHO. 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