3D-QSAR has become a very important tool in the field of Drug Discovery, especially in important areas like
malarial research. The 3D-QSAR is principally a ligand-based drug design but the bioactive conformation of the ligand
can also be taken into account in constructing a 3D-QSAR model. The induction of receptor-based 3D-QSAR has been
proven to give more robust statistical models. In this review, we have discussed the various 3D-QSAR works done so far
which were aimed at combating malaria caused by Plasmodium falciparam. We have also discussed the various
enzymes/receptors (targets) in Plasmodium falciparam for which the 3D-QSAR had been generated. The enzymes - wild
and mutated dihydrofolate reductase, enoyl acyl protein carrier protein reductase, farnesyltransferase, cytochrome bc1, and
falcipains were the major targets for pharmacophore-based drug design. Apart from the above-mentioned targets there
were many scaffolds for which the target macromolecule was undefined and could have single/multiple targets. The
generated 3D-QSAR model can be used to identify hits by screening the pharmacophore against a chemical library. In this
review, the hits identified against various targets of plasmodium falciparam that have been discussed along with their
basic scaffold. The various software programs and chemical databases that have been used in the generation of 3D-QSAR
and screening were given. From this review, we understand that there is a considerable need to develop novel scaffolds
that are different from the existing ligands to overcome cross-resistance.
Keywords: 3D-QSAR, antimalarial targets, malaria, Plasmodium falciparum.
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