1,2-Substituted 4-(1H)-Quinolones: Synthesis, Antimalarial and Antitrypanosomal Activities in Vitro

Molecules

Abraham Wube¹  Antje H࿏ner³  Werner Seebacher³  Marcel Kaiser²  Reto Brun²  Rudolf Bauer¹ 

[1] Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4/1, A-8010 Graz, Austria; E-Mails:;Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland;Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, A-8010 Graz, Austria; E-Mails:

关键词: 4-(1H)-quinolone;    antimalarial;    antitrypanosomal;    cytotoxicity;    SAR;   

DOI  :  10.3390/molecules190914204

来源: mdpi

【 摘 要 】

A diverse array of 4-(1H)-quinolone derivatives bearing substituents at positions 1 and 2 were synthesized and evaluated for antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense, and cytotoxicity against L-6 cells in vitro. Furthermore, selectivity indices were also determined for both parasites. All compounds tested showed antimalarial activity at low micromolar concentrations, with varied degrees of selectivity against L-6 cells. Compound 5a was found to be the most active against P. falciparum, with an IC₅₀ value of 90 nM and good selectivity for the malarial parasite compared to the L-6 cells. Compound 10a, on the other hand, showed a strong antitrypanosomal effect with an IC₅₀ value of 1.25 µM. In this study side chain diversity was explored by varying the side chain length and substitution pattern on the aliphatic group at position-2 and a structure-antiprotozoal activity study revealed that the aromatic ring introduced at C-2 contributed significantly to the antiprotozoal activities.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.