Combination Therapy Strategies for the Treatment of Malaria

Abstract

Malaria is a vector- and blood-borne infection that is responsible for a large number of deaths around the world. Most of the currently used antimalarial therapeutics suffer from drug resistance. The other limitations associated with the currently used antimalarial drugs are poor drug bioavailability, drug toxicity, and poor water solubility. Combination therapy is one of the best approaches that is currently used to treat malaria, whereby two or more therapeutic agents are combined. Different combination therapy strategies are used to overcome the aforementioned limitations. This review article reports two strategies of combination therapy; the incorporation of two or more antimalarials into polymer-based carriers and hybrid compounds designed by hybridization of two antimalarial pharmacophores.

Keywords: antimalarial drugs; combination therapy; hybrid compounds; malaria; polymer-based carriers.

Figure 1

Structures of some antimalarial drugs.

Figure 2

Structure of antimalarial drugs classified based on their chemical structures.

Figure 3

Dihydroartemisinyl-chalcone hybrid compounds 15.

Figure 4

Artemisinin–ferrocene hybrid compounds (16).

Figure 5

Artemisinin–ferrocene hybrid compounds (17).

Figure 6

Artemisinin-based hybrid compounds.

Figure 7

Structure of the artesunate–quinoline-based hybrid compound (23).

Figure 8

Structure of artemisinin–acridine hybrid compounds 24.

Figure 9

Structure of 4-aminoquinoline-triazine hybrid compounds 25a–e.

Figure 10

Structure of 4-aminoquinoline-pyrimidine hybrid compounds.

Figure 11

Structure of 8-aminoquinoline–pyrazolopyrimidine hybrid compounds 27a–d.

Figure 12

Structure of 4-aminoquinoline-purine hybrid compounds 28a–f.

Figure 13

4-aminoquinoline–sulfonamide and hydrazine hybrids 29a–f.

Figure 14

Structure of quinoline–sulfonamide hybrids 30a–f.

Figure 15

Structure of ferrocenylchalcone–b-lactam hybrid compounds 31a–d.

Figure 16

Structure of 3-ferrocenylmethyl-2-hydroxy-1,4-naphthoquinone 32a–f.

Figure 17

Structure of ferrocene–pyrimidine hybrid molecule 33.

Figure 18

A schematic diagram of the Ringsdorf Model of polymer–drug conjugates.

Figure 19

Schematic diagram showing (a) dendrimers loaded with drug and (b) micelles loaded with drug.

Figure 20

Schematic diagram showing hydrogels loaded with drugs.

Figure 21

Schematic diagram showing polymer-encapsulated drug.

Figure 22

Schematic diagram of a liposome loaded with drug.