{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:52:30Z","timestamp":1791183150129,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CONSELHO NACIONAL DE DESENVOLVIMENTO CIENT\u00cdFICO E TECNOL\u00d3GICO","doi-asserted-by":"publisher","award":["404927\/2023\u20108"],"award-info":[{"award-number":["404927\/2023\u20108"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FUNDA\u00c7\u00c3O DE AMPARO \u00c0 PESQUISA DO ESTADO DE S\u00c3O PAULO","doi-asserted-by":"publisher","award":["2019\/19708\u20100"],"award-info":[{"award-number":["2019\/19708\u20100"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Motivated by the antimalarial potential demonstrated by benzamide derivatives of 4\u2010alkylamino\u20107\u2010chloroquinolines against chloroquine\u2010resistant\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    , we designed and synthesized a rational series of\n                    <jats:italic>N<\/jats:italic>\n                    \u20102\u2010(7\u2010chloroquinolin\u20104\u2010ylamino)ethyl amides to investigate the effects of electron\u2010withdrawing and donating substituents on antiplasmodial and cytotoxicity properties, from prediction to in vitro assays. From an initial screening of 22 chloroquine (CQ) analogs, 16 compounds with two distal amino groups in the alkyl linker showed IC\n                    <jats:sub>50<\/jats:sub>\n                    values below 1000\u2009nM against the CQ\u2010sensitive 3D7 strain. Next, their activity against the CQ\u2010resistant K1 strain, in silico toxicity, predicted using the pkCSM program, and in vitro cytotoxicity on HepG2 cells were evaluated. Benzamides containing electron\u2010withdrawing chlorine and nitro groups showed the most promising profiles, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values against the CQ\u2010resistant K1 strain (IC\n                    <jats:sub>50<\/jats:sub>\n                    <jats:sup>K1<\/jats:sup>\n                    , 55\u201372\u2009nM) and resistance index (RI, 0.7\u20131.9) values outperforming CQ (IC\n                    <jats:sub>50<\/jats:sub>\n                    <jats:sup>K1<\/jats:sup>\n                    \u2009=\u2009141\u2009nM, RI\u2009=\u20097.1). Although predicted to be hepatotoxic, these compounds were not cytotoxic to HepG2 cells at the tested concentrations, showing CC\n                    <jats:sub>50<\/jats:sub>\n                    values above 12,500\u2009nM and selectivity indices greater than 115. Compared with CQ, a 3D qualitative SAR model indicated that increased lipophilicity around the distal benzamide moiety enhances antiplasmodial activity against the K1 strain, contributing to the observed potency.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70350","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:27:02Z","timestamp":1791181622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rational Design of\n                    <i>N<\/i>\n                    \u20102\u2010(7\u2010Chloroquinolin\u20104\u2010ylamino)ethyl Amides Active Against Chloroquine\u2010Resistant\n                    <i>Plasmodium falciparum<\/i>"],"prefix":"10.1002","volume":"359","author":[{"given":"Everton P.","family":"Silva","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Bioenergia e S\u00edntese Org\u00e2nica (LPBS), Department of Chemistry Universidade Federal da Para\u00edba (UFPB) Jo\u00e3o Pessoa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila S.","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Parasitology Universidade Federal de S\u00e3o Paulo (UNIFESP) S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C. C.","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Parasitology Universidade Federal de S\u00e3o Paulo (UNIFESP) S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon G.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Institute of Chemistry Universidade Estadual de Campinas (UNICAMP) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago A. M.","family":"Brito","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Multiusu\u00e1rio de Caracteriza\u00e7\u00e3o e An\u00e1lises (LMCA), Instituto de Pesquisa em F\u00e1rmacos e Medicamentos (IPeFarM), UFPB Jo\u00e3o Pessoa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo F. R.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Multiusu\u00e1rio de Caracteriza\u00e7\u00e3o e An\u00e1lises (LMCA), Instituto de Pesquisa em F\u00e1rmacos e Medicamentos (IPeFarM), UFPB Jo\u00e3o Pessoa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helivaldo D. S.","family":"Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Bioenergia e S\u00edntese Org\u00e2nica (LPBS), Department of Chemistry Universidade Federal da Para\u00edba (UFPB) Jo\u00e3o Pessoa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr\u00f4nio F.","family":"Athayde\u2010Filho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Bioenergia e S\u00edntese Org\u00e2nica (LPBS), Department of Chemistry Universidade Federal da Para\u00edba (UFPB) Jo\u00e3o Pessoa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela F.","family":"Fiss","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Bioenergia e S\u00edntese Org\u00e2nica (LPBS), Department of Chemistry Universidade Federal da Para\u00edba (UFPB) Jo\u00e3o Pessoa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-025-11143-4"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.70149"},{"key":"e_1_2_9_4_1","volume-title":"World malaria report 2025: addressing the threat of antimalarial drug resistance","year":"2025"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113865"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115734064318361240827072124"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2025.107097"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2025.1608340"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjc-2023-0062"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202200586"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16121709"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CE00214C"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.21577\/0103-5053.20200223"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/0113852728371713250529122641"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/0109298673372039250614231629"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.5c05060"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm990437l"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020858u"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2025.169090"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00675-10"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2021.04.006"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00104"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci050357s"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2025.141923"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.2307\/3280287"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.48.5.1803-1806.2004"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.5c08663"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.70350","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.70350","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.70350","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:27:04Z","timestamp":1791181624000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.70350"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":28,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/ardp.70350"],"URL":"https:\/\/doi.org\/10.1002\/ardp.70350","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70350"}}