{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:21:03Z","timestamp":1787311263581,"version":"build-2736575974"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation L\u00e9on Fr\u00e9d\u00e9ricq, FRS-FNRS","award":["FC23283"],"award-info":[{"award-number":["FC23283"]}]},{"name":"Fondation L\u00e9on Fr\u00e9d\u00e9ricq, FRS-FNRS","award":["ITMS2014+"],"award-info":[{"award-number":["ITMS2014+"]}]},{"name":"Fondation L\u00e9on Fr\u00e9d\u00e9ricq, FRS-FNRS","award":["313021BUZ3"],"award-info":[{"award-number":["313021BUZ3"]}]},{"name":"UpScale of Comenius University Capacities and Competence in Research, Development and Innovation","award":["FC23283"],"award-info":[{"award-number":["FC23283"]}]},{"name":"UpScale of Comenius University Capacities and Competence in Research, Development and Innovation","award":["ITMS2014+"],"award-info":[{"award-number":["ITMS2014+"]}]},{"name":"UpScale of Comenius University Capacities and Competence in Research, Development and Innovation","award":["313021BUZ3"],"award-info":[{"award-number":["313021BUZ3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A series of seventeen 4-chlorocinnamanilides and seventeen 3,4-dichlorocinnamanilides were characterized for their antiplasmodial activity. In vitro screening on a chloroquine-sensitive strain of Plasmodium falciparum 3D7\/MRA-102 highlighted that 23 compounds possessed IC50 &lt; 30 \u00b5M. Typically, 3,4-dichlorocinnamanilides showed a broader range of activity compared to 4-chlorocinnamanilides. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-en-amide with IC50 = 1.6 \u00b5M was the most effective agent, while the other eight most active derivatives showed IC50 in the range from 1.8 to 4.6 \u00b5M. A good correlation between the experimental logk and the estimated clogP was recorded for the whole ensemble of the lipophilicity generators. Moreover, the SAR-mediated similarity assessment of the novel (di)chlorinated N-arylcinnamamides was conducted using the collaborative (hybrid) ligand-based and structure-related protocols. In consequence, an \u2018averaged\u2019 selection-driven interaction pattern was produced based in namely \u2018pseudo\u2013consensus\u2019 3D pharmacophore mapping. The molecular docking approach was engaged for the most potent antiplasmodial agents in order to gain an insight into the arginase-inhibitor binding mode. The docking study revealed that (di)chlorinated aromatic (C-phenyl) rings are oriented towards the binuclear manganese cluster in the energetically favorable poses of the chloroquine and the most potent arginase inhibitors. Additionally, the water-mediated hydrogen bonds were formed via carbonyl function present in the new N-arylcinnamamides and the fluorine substituent (alone or in trifluoromethyl group) of N-phenyl ring seems to play a key role in forming the halogen bonds.<\/jats:p>","DOI":"10.3390\/ijms24043611","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T03:28:46Z","timestamp":1676258926000},"page":"3611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Towards Arginase Inhibition: Hybrid SAR Protocol for Property Mapping of Chlorinated N-arylcinnamamides"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9842-1289","authenticated-orcid":false,"given":"Andrzej","family":"Bak","sequence":"first","affiliation":[{"name":"Institute of Chemistry, University of Silesia, Szkolna 9, 40-007 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3589-4361","authenticated-orcid":false,"given":"Jiri","family":"Kos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic"},{"name":"Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Degotte","sequence":"additional","affiliation":[{"name":"I2BM, Department of Molecular Chemistry, University Grenoble-Alpes, Rue de la Chimie 570, 38610 Gieres, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Swietlicka","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, University of Silesia, Szkolna 9, 40-007 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-5424","authenticated-orcid":false,"given":"Tomas","family":"Strharsky","sequence":"additional","affiliation":[{"name":"Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palackeho 1946\/1, 612 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Pindjakova","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3712-8641","authenticated-orcid":false,"given":"Tomas","family":"Gonec","sequence":"additional","affiliation":[{"name":"Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palackeho 1946\/1, 612 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-7546","authenticated-orcid":false,"given":"Adam","family":"Smolinski","sequence":"additional","affiliation":[{"name":"GiG Research Institute, Pl. Gwarkow 1, 40-166 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Francotte","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry, CIRM, Department of Pharmacy, University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0770-9990","authenticated-orcid":false,"given":"Michel","family":"Frederich","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacognosy, CIRM, Department of Pharmacy, University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violetta","family":"Kozik","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, University of Silesia, Szkolna 9, 40-007 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2003-9052","authenticated-orcid":false,"given":"Josef","family":"Jampilek","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia"},{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 845 10 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1172\/JCI33996","article-title":"Malaria: Progress, perils, and prospects for eradication","volume":"118","author":"Greenwood","year":"2008","journal-title":"J. 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