Chloroquine-enhancing activity

A preliminary conclusion that stems from the critical analysis of these results is that many Strychnos alkaloids and probably the aspidosperman indole alkaloids may reverse in vitro chloroquine resistance with different degrees of activity. Instead of testing all of these alkaloids, it would be now useful to determine the minimal structure requirement for in vitro and in vivo chloroquine-enhancing activity. 

Khan, M.A., et al. 2005. Enhanced anticryptococcal activity of chloroquine in phosphatidylserine-containing liposomes in a murine model. J Antimicrob Chemother 55 223. 

Ferroquine possesses planar chirality due to the non-symmetrical 1,2-substitution of the ferrocene entity, and the pure enantiomers (+)35 and (—)35 were obtained by enzymatic resolution using the Candida rugosa lipase as a biocatalyst. The enantiomeric purity levels exceed 98%. However, the two optical isomers display identical activity in vitro at the nanomolecular level. In vivo, however, either of the enantiomers alone is less active than the racemic mixture against both chloroquine-sensitive and chloroquine-resistant strains. In addition, (4-)35 displays better curative effects than (—)35, suggesting different pharmacokinetic properties. The reasons for the enhanced behavior of racemic ferroquine have not yet been elucidated. It is still not clear whether 35 is oxidized by the parasite to give the ferricinium ion, thus initiating Fenton-type reactivity. Such a hypothesis is reasonable, given that reactive oxidative species can escalate in cancer cells due to the malfunction of mitochondria. ... 

FIGURE 6.19 Transfection efficiency (quantified as relative light units [RLU]/mg protein) of three different SLN formulations (all made from 4% cetyl pahnitate, 2% Tween 80/Span 85 [7 3], and 0.5% [S0.5], and 1.0% [SI] or 2.0% [S2] of the cationic hpid DOTAP) without medium (Medium) and with medium and 100 piM chloroquine phosphate (Med. + 100 J,M QC). The chloroquine addition enhanced transfection activity for all tested SLN in different extends. 

The interplay of antiparasitic drugs and metal complexes may give a synergistic effect and the way activity is affected is shown by the unusual result that a chloroquine adduct of rhodium acetate, Rh2-(acetate)4(chloroquine)], is more active in vitro in T, rhodesiense than either component [98]. This complex is also as active in malaria in vivo as the free chloroquine, although no enhancement over free drug is seen [98]. An interesting historical note to the metallation of trypanocidal drugs is that the platinum salt of Salvarsan was reported by Ehrlich in 1915 in one of his last papers [99]. 

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