Synthesis, in vitro antiplasmodial and antiproliferative activities of a series of quinoline-ferrocene hybrids
Abstract
Series of quinoline–ferrocene hybrids containing
various linkers were synthesized and evaluated for
antimalarial and anticancer activities as well as cytotoxicity.
The hybrids with rigid linkers were found to be inactive,
while those with flexible spacers showed activity against
both the D10 and Dd2 strains of Plasmodium falciparum, and
demonstrated a good selectivity towards these parasitic cells
in comparison with emetine. The hybrid 16, featuring
3-aminopropyl methylamine linker, was the most antimalarial
active compound, exhibiting a significantly better
potency than chloroquine against the Dd2 strain
(IC50 = 0.008 vs. 0.148 lM; 19-fold), and was also found to
be significantly more active than the equimolar chloroquine–
ferrocene combination (IC50 = 3.7 vs. 41 ng/ml, tenfold)
against the Dd2 strain. Anticancer activity screening showed
that all the antimalarial active hybrids also exhibited potent
cytostatic (GI50 = 0.6–3.3 lM) and had good cytotoxic
effects (LC50 = 6–8 lM) against all three cancer cell lines.
The hybrid 11 possessing 1,4-butanediamine linker was
distinctively the most antiproliferative of all. It was found to
be more cytostatic (GI50: 0.7 vs. 5.9 lM, eightfold) and
(LC50: 6.4 vs. 92.6 lM, 14-fold) more cytotoxic than etoposide
against the TK10 (renal) cell line.
URI
http://hdl.handle.net/10394/14850https://link.springer.com/article/10.1007/s00044-013-0748-4
https://doi.org/10.1007/s00044-013-0748-4
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