. Conclusions
Improved vector control, awareness of malaria and a more
prudent approach towards antimalarial drugs have all contributed
to a decrease in the number of malaria cases over the last ten years.
However, emerging resistance to all known antimalarial agents is
an increasing problem and as such, there is a continued need for
novel compounds bearing antimalarial properties. Against this
backdrop hybrid drugs, containing two or more motifs that have
biological activity, have emerged as a new and important area of
research. The ART-QN hybrid 2 is established as a significant
contribution to this field.
In designing hybrid drugs, a number of key features have been
noted. The new compounds sometimes show decreased antimalarial
activity with respect to QN, CQ, PQ or ARTs, but trends within
groups of molecules reveal useful structure-activity relationships,
which aid the design and synthesis of subsequent generations of
potential antimalarial compounds.
The linker between the two components of a hybrid drug plays
an important role in whether or not the target molecule retains its
biological activity. In addition, the basicity of the hybrid molecule
can determine whether or not it is able to accumulate in the acidic
environment of the DV. Where pKa values are known, it has been
observed that compounds with a lower pKa show a concomitant
decrease in antimalarial activity.
Finally, an understanding of the mechanisms involved in the
development of resistance is key to the design of new antimalarial
agents. In this respect hybrid molecules having more than one
mode of action may prove to be particularly important, and they are
expected to make substantial contri