In vitro anti-malarial activity studies were carried out in
Plasmodium falciparum parasite, using a chloroquine-susceptible (CQS) strain (3D7) and chloroquine-resistant (CQR) strain (W2); the results are given in Table
2. The anti-malarial drug CQDP was used as a reference. All tested metal-CQ and metal-CQDP complexes displayed very high anti-malarial activity against the CQS strain (3D7), in general all metal complexes showed better activity than CQDP, except Pd(CQDP)
2I
2 which showed the less activity (IC
50 = 24 nM). Suggesting that, metals like gold and platinum achieved to improve the antiplasmodial activity of CQDP. However, this trend was not observed when the studied metal complexes were tested against the CQR strain (W2), the result revealed that Pt(CQDP)
2Cl
2 was the most active compound (IC
50 = 89 nM) of these series, followed by Au(CQ)(TaTg) and Pt(CQDP)
2I
2 which displayed similar antiplasmodial activity IC
50 = 175 nM and IC
50 = 177 nM respectively; these three complexes were clearly more active that CQDP (IC
50 = 406 nM), the rest of the studied metal complexes were less active than CQDP, although not clear trend was observed, it is noticeable that Pt(CQDP)
2Cl
2 was the most active complex against CQS and CQR. The IC
50 values found in the 3D7 CQS strain are equivalent to those found in CQS laboratory strains or field isolates for the ferroquine, the 7-chloro-4-[(2-N,N-dimethylaminomethyl)ferrocenyl-methylamino]quinoline, ruthenoquine or 2-phenylindoles and 3-ferrocenylmethyl-2-phenylindoles but those obtained in the W2 CQR strain are higher than those found in CQR laboratory strains or field isolates for the two metalloquines [
28‐
32]. However, the
in vitro activity of these different compounds exhibited higher activity than those in the micromolar range obtained with pyrazole palladium or platinum complexes [
33], rhenium-4-aminoquinolines [
34], ferrocene-ciprofloxacin complexes [
35,
36] and ferrocenyl-chalcones [
37]. All tested metal complexes are more active against CQS than CQR. These data suggest that the activity of present compounds is correlated with that of CQ. Previous studies suggested that metal coordination to CQ reduces or abolished cross-resistance [
28,
31]. The ferroquine and ruthenoquine were correlated to each other but not with CQ, confirming the lack of cross-resistance. However, in some works, some rhenium bioorganometallics based on the 4-aminoquinoline structure were less active
in vitro against the W2 CQR strain than the 3D7 CQS [
34]. A larger number of strains with several susceptibility profiles should be necessary to properly assess the cross-resistance between the present compounds and CQ and conclude.
Table 2
In vitro
antimalarial activity and interaction with hemin, inhibition of β-hematin formation
(1) Au(CQ)(Cl) | 10 (1.80) | 483 (0.84) | 4.76 ± 0.20 | + | 0.82 ± 0.04 (0.2) | 0.99 ± 0.08 (2.3) |
(2) Au(CQ)(TaTg) | 15 (1.20) | 175 (2.32) | 4.63 ± 0.03 | + | 0.75 ± 0.05 (0.2) | 2.32 ± 0.11 (0.9) |
(3) Pt(CQDP)2(Cl)2 | 7 (2.57) | 89 (4.56) | 4.89 ± 0.10 | + | 1.88 ± 0.11 (0.1) | 2.09 ± 0.61 (1.1) |
(4) Pt(CQDP)2(I)2 | 10 (1.80) | 177 (2.29) | 4.85 ± 0.09 | + | 0.52 ± 0.06 (0.3) | 1.86 ± 0.06 (1.2) |
(5) Pd(CQ)2(Cl)2 | 12 (1.50) | 653 (0.62) | 4.09 ± 0.04 | + | 0.46 ± 0.02 (0.3) | 1.88 ± 0.81 (1.2) |
(6) Pd(CQDP)2(I)2 | 24 (0.75) | 608 (0.67) | 4.45 ± 0.02 | + | 0.34 ± 0.08 (0.4) | 2.21 ± 0.12 (1.0) |
CQDP | 18 (−−) | 406 (−−) | 5.01 ± 0.01 | + | 0.15 ± 0.03 (1) | 2.23 ± 0.09 (1.0) |