Vandekerckhove S., Van Herreweghe S., Willems J., Danneels B., Desmet T., De Kock C., Smith P.J., Chibale K., D'Hooghe M.
SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, Ghent, Belgium; Centre for Industrial Biotechnology and Biocatalysis, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, Ghent, Belgium; Division of Pharmacology, University of Cape Town, Groote Schuur Hospital, Observatory, South Africa; South African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry, University of Cape Town, Rondebosch, South Africa
Vandekerckhove, S., SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, Ghent, Belgium; Van Herreweghe, S., SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, Ghent, Belgium; Willems, J., SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, Ghent, Belgium; Danneels, B., Centre for Industrial Biotechnology and Biocatalysis, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, Ghent, Belgium; Desmet, T., Centre for Industrial Biotechnology and Biocatalysis, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, Ghent, Belgium; De Kock, C., Division of Pharmacology, University of Cape Town, Groote Schuur Hospital, Observatory, South Africa; Smith, P.J., Division of Pharmacology, University of Cape Town, Groote Schuur Hospital, Observatory, South Africa; Chibale, K., South African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry, University of Cape Town, Rondebosch, South Africa; D'Hooghe, M., SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, Ghent, Belgium
(3-Pyrrolin-1-yl)- and (2-oxopyrrolidin-1-yl)quinolines were prepared via cyclization of diallylaminoquinolines and 4-chloro-N-quinolinylbutanamides, respectively, as novel synthetic intermediates en route to N-functionalized 3-, 5-, 6- and 8-aminoquinolines with potential biological activity. (3-Pyrrolin-1-yl)quinolines were subjected to bromination reactions, and the reactivity of (2-oxopyrrolidin-1-yl)quinolines toward lithium aluminum hydride and methyllithium was assessed, providing an entry into a broad range of novel functionalized (pyrrolidin-1-yl)- and (hydroxyalkylamino)quinolines. Antiplasmodial evaluation of these novel quinolines and their functionalized derivatives revealed moderate micromolar potency against a chloroquine-sensitive strain of the malaria parasite Plasmodium falciparum, and the two most potent compounds also showed micromolar activity against a chloroquine-resistant strain of P. falciparum. Antifungal assessment of (hydroxyalkylamino)quinolines revealed three compounds with promising MIC values against Rhodotorula bogoriensis and one compound with potent activity against Aspergillus flavus. © 2014 Elsevier Masson SAS. All rights reserved.