Contrasting Effect of Salts on the Binding of Antimalarial Drug Hydroxychloroquine with Different Sequences of Duplex DNA.

Hydroxychloroquine (HCQ) is an important antimalarial drug which functions plausibly by targeting the DNA of parasites. Salts play a crucial role in the functionality of various biological processes. Hence, the effect of salts (NaCl and MgCl 2 ) on the binding of HCQ with AT- and CG-DNAs as well as the binding-induced stability of both sequences of DNAs have been investigated using the spectroscopic and molecular dynamics (MD) simulation methods. It has been found that the effect of salts on the binding of HCQ is highly sensitive to the nature of ions as well as DNA sequences. The effect of ions is opposite for the binding of AT- and CG-DNAs as the presence of Mg 2+ ions enhances the binding of HCQ with AT-DNA, whereas the binding of HCQ with CG-DNA gets decreased on the addition of both ions. Similarly, the presence of Mg 2+ enhances the stabilization of HCQ-bound AT-DNA, whereas the effect is opposite for the CG-DNA in the presence of both the ions. The MD simulation study suggests that the hydration states of both ions are different and they interact differently in the minor and major grooves of both the sequences of DNA which may be one of the reasons for the different binding of HCQ with these two sequences of DNA in the presence of salts. The information about the effect of salts on the binding of HCQ with DNAs in a sequence-specific manner may be useful in understanding the mechanism of the action and toxicity effect of HCQ against malaria.