{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:41:44Z","timestamp":1780548104671,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T00:00:00Z","timestamp":1386633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Herein, we report the antimalarial activity of nine 4-methoxychalcone derivatives 1a\u2013i and an initial analysis of their ADMET properties. All compounds showed potent activity against the P. falciparum chloroquine-resistant clone W2, with IC50 values ranging from 1.96 \u00b5M to 10.99 \u00b5M, with moderate or low cytotoxicity against the HeLa cell line. The compound 1a (IC50 = 2.06 \u00b5M) had the best selectivity index (9.0). All the sulfonamide 4-metychalcone derivatives synthesized had cLogP values between 2 and 5 (mean value 3.79) and molecular weights (MWs) below 500. The substitution of the pyrrolidine group in 1i by a morpholine group in 1a reduced the cLogP value from 3.05 in compound 1i to 2.34 in compound 1a. Indeed, compound 1a had the highest LipE value. The binding free energy of compound 1a showed it to be the most optimal chalcone derivative for plasmepsin-2 (\u22127.3 Kcal\/mol). The physicochemical properties and LipE analysis of the dataset allowed us to establish that compound 1a is the highest quality compound of the series and a potential oral lead candidate.<\/jats:p>","DOI":"10.3390\/molecules181215276","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T12:32:12Z","timestamp":1386678732000},"page":"15276-15287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Antimalarial Activity of 4-Metoxychalcones: Docking Studies as Falcipain\/Plasmepsin Inhibitors, ADMET and Lipophilic Efficiency Analysis to Identify a Putative Oral Lead Candidate"],"prefix":"10.3390","volume":"18","author":[{"given":"Michael","family":"De Oliveira","sequence":"first","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade-UFSJ\/Campus Centro-Oeste, CEP 35501-296, Divin\u00f3polis, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele","family":"Cenzi","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade-UFSJ\/Campus Centro-Oeste, CEP 35501-296, Divin\u00f3polis, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Nunes","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade-UFSJ\/Campus Centro-Oeste, CEP 35501-296, Divin\u00f3polis, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Andrighetti","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias da Sa\u00fade-UFMT\/Campus Sinop, CEP 78557-267, Sinop, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denia","family":"De Sousa Valad\u00e3o","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias da Sa\u00fade-UFMT\/Campus Sinop, CEP 78557-267, Sinop, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia","family":"Dos Reis","sequence":"additional","affiliation":[{"name":"Departmento de Ci\u00eancias Farmac\u00eauticas-UFSC\/Campus Universit\u00e1rio Trindade, CEP 88040-900, Florian\u00f3polis, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Departmento de Ci\u00eancias Farmac\u00eauticas-UFSC\/Campus Universit\u00e1rio Trindade, CEP 88040-900, Florian\u00f3polis, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Nunes","sequence":"additional","affiliation":[{"name":"Departmento de Qu\u00edmica-UFSC\/Campus Universit\u00e1rio Trindade, CEP 88040-900, Florian\u00f3polis, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moacyr","family":"J\u00fanior","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias 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