Accessibility navigation


Synthesis, structural determination, and pharmacology of putative dinitroaniline antimalarials

Casino, A. d., Lukinović, V., Bhatt, R., Randle, L. E., Dascombe, M. J., Fennell, D. B. J., Drew, M. G. B., Bell, A., Fielding, A. J. and Ismail, F. M. D. (2018) Synthesis, structural determination, and pharmacology of putative dinitroaniline antimalarials. ChemistrySelect, 3 (26). pp. 7572-7580. ISSN 2365-6549

Full text not archived in this repository.

It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.1002/slct.201801723

Abstract/Summary

A series of novel, homologous compounds possessing the general formula N1‐Nn‐bis(2,6‐dinitro‐4‐trifluormethylphenyl)‐1,n‐diamino alkanes (where n=4, 6, 10 or 12), were designed to probe inter‐ and intra‐ binding site dimensions in malarial parasite (Plasmodium) tubulin. Various crystal structures, including chloralin and trifluralin, an isopropyl dimer, and 2,6‐dinitro‐4‐trifluoromethyl‐phenylamine, were determined. Dinitroanilines, when soluble, were evaluated both in culture and in vivo. Trifluralin was up to 2‐fold more active than chloralin against cultured parasites. The isopropyl dimer was water soluble (>5 mM) and revealed activity superior to that of chloralin in culture. The effects of selected dinitroanilines upon the mitotic microtubular structures of Plasmodium, the putative target of these dinitroanilines, were also determined. Electronic properties of the molecules were calculated using DFT (B3LYP/6‐31+G* level) to ascertain whether incorporation of such a pharmacophore could allow both QSAR and rational development of more selectively toxic antiparasitic agents.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
ID Code:78331
Publisher:Wiley

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation