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Spectral Assignments and Reference Data, The 1H and 13C NMR resonances of 22 1-alkyl-pyrazole and 25 1-alkyl-pyrazoline derivatives were assigned completely using the concerted application of one- and two-dimensional experiments (DEPT, gs-HMQC and gs-HMBC). Nuclear Overhauser enhancement (NOE) effects, conformational analysis and X-ray crystallography confirm the preferred conformation of those compounds., This work was partially supported by grants from theMinisterio de CienciayTecnología(SAF2005-07991-C02-01andSAF2005-07991- C02-02) and from the Junta de Andalucia (P06-CTS-01941). Duane Choquesillo-Lazarte thanks Consejo Superior Investigaciones Cientificas – European Union for an I3P postdoctoral research contract

In this article we present a series of non-cytotoxic potent human choline kinase (CK) inhibitors that exhibit nanomolar antiplasmodial activity in vitro. The most active antiplasmodial compounds, 10a-b, bearing a pyridinium cationic head were inactive against CK, while compounds 10g and 10j with a quinolinium moiety exhibit moderate inhibition of both the parasite and the enzyme. The results point towards an additional mechanism of action unrelated to CK inhibition that remains to be established., This work was funded by the University of Granada, Cei-Biotic Project CEI2013-MP-1; the Junta de Andalucia (BIO-199); the Plan Nacional de Investigacion Cientifica, Instituto de Salud Carlos III-Subdireccion General de Redes y Centros de Investigacion Cooperativa-Red de Investigacion Cooperativa en Enfermedades Tropicales (RICET: RD16/0027/0014); and the Plan Nacional (SAF2016-79957-R).

This research work was supported by Ministerio de Ciencia e Innovacion (PID2019-109294RB-100) Project. This research was also aided by the Andalusian regional government (CTS-236), B-CTS-216-UGR20 project and by the University of Perugia. Alberto Sola-Leyva holds a Formacion de Doctores 2018 grant (ref. PRE2018-085440) from the Ministerio de Ciencia, Innovacion y Universidades (Spain). Pilar M. Luque-Navarro holds a grant from Ministero dellIstruzione (Italy). Emilio Parisini acknowledges the European Regional Development Fund (ERDF) project BioDrug (No. 1.1.1.5/19/A/004) and the Latvian Council of Science (grant No. lzp-2020/2-0013) for financial support., A large number of different types of cancer have been shown to be associated with an abnormal metabolism of phosphatidylcholine (PC), the main component of eukaryotic cell membranes. Indeed, the overexpression of choline kinase alpha 1 (ChoK alpha 1), the enzyme that catalyses the bioconversion of choline to phosphocholine (PCho), has been found to associate with cell proliferation, oncogenic transformation and carcinogenesis. Hence, ChoK alpha 1 has been described as a possible cancer therapeutic target. Moreover, the choline transporter CTL1 has been shown to be highly expressed in several tumour cell lines. In the present work, we evaluate the antiproliferative effect of PL48, a rationally designed inhibitor of ChoK alpha 1, in MCF7 and HepG2 cell lines. In addition, we illustrate that the predominant mechanism of cellular choline uptake in these cells is mediated by the CTL1 choline transporter. A possible correlation between the inhibition of both choline uptake and ChoK alpha 1 activity and cell proliferation in cancer cell lines is also highlighted. We conclude that the efficacy of this inhibitor on cell proliferation in both cell lines is closely correlated with its capability to block choline uptake and ChoK alpha 1 activity, making both proteins potential targets in cancer therapy., Instituto de Salud Carlos III, Spanish Government, European Commission PID2019-109294RB-100, Andalusian regional government CTS-236 B-CTS-216-UGR20, Spanish Government PRE2018-085440, European Regional Development Fund (ERDF) project BioDrug 1.1.1.5/19/A/004, Latvian Ministry of Education and Science lzp-2020/2-0013