{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T03:23:40Z","timestamp":1785813820613,"version":"3.56.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This paper reports a series of nine hybrid compounds of 7\u2010substituted 4\u2010aminoquinoline and cinnamic acid as antiplasmodial agents. <jats:sup>1<\/jats:sup>H NMR and <jats:sup>13<\/jats:sup>C NMR spectroscopic analysis and mass spectrometry studies were used to confirm the structures. The synthesized compounds were moderately active, with IC<jats:sub>50<\/jats:sub> values ranging from <jats:bold>1.8<\/jats:bold> to <jats:bold>16<\/jats:bold>\u00a0\u00b5M against the <jats:italic>Pf<\/jats:italic>3D7 chloroquine\u2010sensitive strain in vitro. Compound <jats:bold>C11<\/jats:bold> was shown to be the most potent in this investigation, with an IC<jats:sub>50<\/jats:sub> value of <jats:bold>1.8<\/jats:bold>\u00a0\u00b5M. Molecular docking studies revealed that compounds <jats:bold>C14<\/jats:bold> and <jats:bold>C17<\/jats:bold>, with binding energies  of <jats:bold>\u22127.19<\/jats:bold> and <jats:bold>\u22127.72<\/jats:bold>\u00a0kcal\/mol and inhibition constants (<jats:italic>K<jats:sub>i<\/jats:sub><\/jats:italic>) of <jats:bold>5.36<\/jats:bold> and <jats:bold>2.20<\/jats:bold>\u00a0\u00b5M, respectively, were the best inhibitor candidates. The results of the Frontier molecular orbitals revealed that compounds possessed a small HOMO\u2013LUMO energy gap. The HOMO\u2013LUMO energy distributions indicated that the cinnamic acid regions favored the LUMO distribution, while the quinoline regions favored the HOMO energy. The investigation of absorption, distribution, metabolism, excretion, and toxicity based on in silico ADME tools predicted that the compounds have a good drug\u2010like character.<\/jats:p>","DOI":"10.1111\/cbdd.14050","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T21:10:36Z","timestamp":1648761036000},"page":"41-50","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synthesis, <i>in silico<\/i> docking studies, and antiplasmodial activity of hybrid molecules bearing 7\u2010substituted 4\u2010aminoquinoline moiety and cinnamic acid derivatives"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7923-3709","authenticated-orcid":false,"given":"Fostino R. B.","family":"Bokosi","sequence":"first","affiliation":[{"name":"Department of Chemistry Faculty of Science University of Malawi  Zomba Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7682-9489","authenticated-orcid":false,"given":"Mpho P.","family":"Ngoepe","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Science University of South Africa  Florida South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2018.10.002"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037259"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202000331"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2021.127855"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1473\u20103099(19)30261\u20100"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.055"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20103305\u20103\u20105"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25071571"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.07.064"},{"key":"e_1_2_8_11_1","first-page":"73","volume-title":"Annual reports in medicinal chemistry","author":"Gupta P.","year":"2019"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107672"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115973"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3073"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm301654b"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2012.05.022"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201200257"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/japtr.JAPTR_178_19"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15010060"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044\u2010017\u20102090\u20108"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165712"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25010066"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03342"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.1.235\u2010254.2004"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/322858"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199609123351107"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci21682"},{"key":"e_1_2_8_29_1","volume-title":"World malaria report","author":"WHO","year":"2021"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2007.04.007"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.14050","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.14050","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.14050","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T12:19:50Z","timestamp":1692879590000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.14050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,11]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1111\/cbdd.14050"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.14050","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,11]]},"assertion":[{"value":"2022-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}