Chemistry and Structures of Plant Derived Antimalarials and Their Semi-synthetic Analogues

Natural compounds, mostly from plants, are a potential source of antimalarial drugs due to presence of various secondary metabolites with variety of structures and different biological activities. Amongst the secondary plant metabolites, quassinoids, sesquiterpene lactone and alkaloids are the most important metabolites with diverse bio-potencies. Therefore, due to the wide use of alkaloid derived drugs, antimalarials can be grouped into two groups: alkaloidal antimalarials and nonalkaloidal antimalarials. By virtue of their chemical structure, the alkaloidal antimalarials are further classified into various classes (Bisbenzylisoquinolines, azaanthracene alkaloids, protoberberine and aporphine-benzylisoquinolines, morphinan alkaloids, naphthylisoquinolines, indoloquinolone alkaloids, indole alkaloids, benzofenantridine, furoquinolines and acridone, tetrahydroquinolines etc.). Apart from the bio-potency of the alkaloids, some other chemical entities (non-alkaloidal) show marked antimalarial activity which includes tannins, quassinoids, sesquiterpene lactones, limonoids, flavonoids, chromones, xanthones, quinones and other miscellaneous phenolic compounds and related compounds. This compilation covers most of recently published alkaloidal and non-alkaloidal antimalarial natural compounds with antiplasmodial and antimalarial properties published over last two decades. The structure, chemistry and evaluation of antimalarial activity of the compounds by in vitro and in vivo assays have been highlighted. Several patents published focusing on the phenyacetonitrile, bisquinoline, 4-amino quinoline, spiro and dispiro-1,2,4- trioxolane, phenyl(thio)urea deoxythymidine moieties as potent antimalarials have also been discussed in the current study. Besides, this review article also compiles the promising antimalarial compounds patented during the last two decades.

Keywords: Artemisinin, Alkaloids, Antimalarial, Flavonoids, Malaria, Quinine.