{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:45:03Z","timestamp":1781113503191,"version":"3.54.1"},"reference-count":29,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Convocatoria 2019 Proyectos de I + D + i - RTI Tipo B \u201cMinisterio de Ciencia e Innovaci\u00f3n\u201d","award":["PID2019-109294RB-I00"],"award-info":[{"award-number":["PID2019-109294RB-I00"]}]},{"name":"University of Granada, Cei-BioticProject grant number","award":["CEI2013-MP-1"],"award-info":[{"award-number":["CEI2013-MP-1"]}]},{"name":"the Instituto de Salud Carlos III Subdireccio\u0301n General de Redes y Centros de Investigacio\u0301n Cooperativa-Red de Investigacio\u0301n Cooperativa en Enfermedades Tropicales","award":["RICET:RD16\/0027\/0014"],"award-info":[{"award-number":["RICET:RD16\/0027\/0014"]}]},{"name":"the Plan Nacional","award":["SAF PID2019-109623RB-I002016-79957-R"],"award-info":[{"award-number":["SAF PID2019-109623RB-I002016-79957-R"]}]},{"name":"the Junta de Andaluc\u00eda","award":["BIO-199"],"award-info":[{"award-number":["BIO-199"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>In the fight against Malaria, new strategies need to be developed to avoid resistance of the parasite to pharmaceutics and other prevention barriers. Recently, a Host Directed Therapy approach based on the suppression of the starting materials uptake from the host by the parasite has provided excellent results. In this article, we propose the synthesis of bioisosteric compounds that are capable of inhibiting Plasmodium falciparum Choline Kinase and therefore to reduce choline uptake, which is essential for the development of the parasite. Of the 41 bioisosteric compounds reported herein, none showed any influence of the linker on the antimalarial and enzyme inhibitory activity, whereas an effect of the type of cationic heads used could be observed. SARs determined that the thienopyrimidine substituted in 4 by a pyrrolidine is the best scaffold, independently of the chosen linker. The decrease in lipophilicity seems to improve the antimalarial activity but to cause an opposite effect on the inhibition of the enzyme. While potent compounds with similar good inhibitory values have been related to the proposed mechanism of action, some of them still show discrepancies and further studies are needed to determine their specific molecular target.<\/jats:p>","DOI":"10.3390\/pharmaceutics13111842","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T22:17:23Z","timestamp":1635891443000},"page":"1842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["New Compounds with Bioisosteric Replacement of Classic Choline Kinase Inhibitors Show Potent Antiplasmodial Activity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5274-7219","authenticated-orcid":false,"given":"Francisco Jos\u00e9","family":"Aguilar-Troyano","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archimede","family":"Torretta","sequence":"additional","affiliation":[{"name":"Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, Via Pascoli 70\/3, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Rubbini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Fasiolo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar Mar\u00eda","family":"Luque-Navarro","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1300-5196","authenticated-orcid":false,"given":"Mar\u00eda Paz","family":"Carrasco-Jimenez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Sciences, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiomar","family":"P\u00e9rez-Moreno","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology, Institute of Parasitology and Biomedicine \u201cL\u00f3pez-Neyra\u201d, Spanish National Research Council, Parque Tecnol\u00f3gico de Ciencias de la Salud, Avenida del Conocimiento 17, 18016, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bosch-Navarrete","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology, Institute of Parasitology and Biomedicine \u201cL\u00f3pez-Neyra\u201d, Spanish National Research Council, Parque Tecnol\u00f3gico de Ciencias de la Salud, Avenida del Conocimiento 17, 18016, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Gonz\u00e1lez-Pacanowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology, Institute of Parasitology and Biomedicine \u201cL\u00f3pez-Neyra\u201d, Spanish National Research Council, Parque Tecnol\u00f3gico de Ciencias de la Salud, Avenida del Conocimiento 17, 18016, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5529-0039","authenticated-orcid":false,"given":"Emilio","family":"Parisini","sequence":"additional","affiliation":[{"name":"Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, Via Pascoli 70\/3, 20133 Milano, Italy"},{"name":"Department of Organic Synthesis, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1142-6448","authenticated-orcid":false,"given":"Luisa Carlota","family":"Lopez-Cara","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"World Health Organization (2020). 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