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A good correlation (r<jats:sup>2<\/jats:sup>=0.64, P=0.017) between adsorption energies and the logarithm of \u03b2\u2010hematin inhibitory activity was found for this face. Of 53 monocyclic, bicyclic and tricyclic scaffolds, the latter yielded the most favorable adsorption energies. Five new amino\u2010phenoxazine compounds were pursued as \u03b2\u2010hematin inhibitors based on adsorption behaviour. The 2\u2010substituted phenoxazines show good to moderate \u03b2\u2010hematin inhibitory activity (&lt;100\u2005\u03bcM) and <jats:italic>Plasmodium falciparum<\/jats:italic> blood stage activity against the 3D7 strain. <jats:italic>N<\/jats:italic><jats:sup>1<\/jats:sup><jats:italic>,N<\/jats:italic><jats:sup>1<\/jats:sup>\u2010diethyl\u2010<jats:italic>N<\/jats:italic><jats:sup>4<\/jats:sup>\u2010(10<jats:italic>H<\/jats:italic>\u2010phenoxazin\u20102\u2010yl)pentane\u20101,4\u2010diamine (<jats:bold>P2a<\/jats:bold>) is the most promising hit with IC<jats:sub>50<\/jats:sub> values of 4.7\u00b10.6 and 0.64\u00b10.05\u2005\u03bcM, respectively. Adsorption energies are predictive of \u03b2\u2010hematin inhibitory activity, and thus the <jats:italic>in silico<\/jats:italic> approach is a beneficial tool for structure\u2010based development of new non\u2010quinoline inhibitors.<\/jats:p>","DOI":"10.1002\/cmdc.202200139","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T08:51:28Z","timestamp":1649235088000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Adsorption to the Surface of Hemozoin Crystals: Structure\u2010Based Design and Synthesis of Amino\u2010Phenoxazine \u03b2\u2010Hematin Inhibitors"],"prefix":"10.1002","volume":"17","author":[{"given":"Tania","family":"Olivier","sequence":"first","affiliation":[{"name":"Department of Chemistry and Polymer Science Stellenbosch University  Private BagX1 Matieland 7602 South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Loots","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Polymer Science Stellenbosch University  Private BagX1 Matieland 7602 South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e9lle","family":"Kok","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Stellenbosch University  Private BagX1 Matieland 7602 South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6233-3498","authenticated-orcid":false,"given":"Marianne","family":"de Villiers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Stellenbosch University  Private BagX1 Matieland 7602 South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janette","family":"Reader","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Genetics and Microbiology Institute for Sustainable Malaria Control University of Pretoria  Pretoria 0028 South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5888-2905","authenticated-orcid":false,"given":"Lyn\u2010Mari\u00e9","family":"Birkholtz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Genetics and Microbiology Institute for Sustainable Malaria Control University of Pretoria  Pretoria 0028 South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-123X","authenticated-orcid":false,"given":"Gareth E.","family":"Arnott","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Polymer Science Stellenbosch University  Private BagX1 Matieland 7602 South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2932-395X","authenticated-orcid":false,"given":"Katherine A.","family":"de Villiers","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Polymer Science Stellenbosch University  Private BagX1 Matieland 7602 South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33080-5"},{"key":"e_1_2_8_2_1","unstructured":"World Malaria Report 2021 World Health Organization 2021. 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