Malaria continues to endanger over half of the world's population, claiming
1-2 million lives each year. The main causative agents are Plasmodium falciparum (Pf)
and Plasmodium vivax (Pv). Both cause widespread mortality and morbidity, and they
impose a significant socioeconomic burden, particularly in poor nations. The
emergence and dissemination of resistance to currently available antimalarial
medications have generated a crisis scenario among experts. Unfortunately,
artemisinin-resistant parasitic strains have been observed in Southeast Asia. Several
approaches that include, combination therapy, exploitation of natural products, drug
resistance reversers, covalent bitherapy, identification of novel targets, and
development of vaccines, have been explored to surmount the issue of drug resistance.
In the absence of effective vaccinations, the disease has been mostly managed with
chemotherapy and chemoprophylaxis. Over the past year, breakthroughs in technology
such as molecular evolutionary and population genetic techniques have exposed the
malaria parasite genome, considerably contributing to the understanding of the targets
and dissemination of parasite treatment resistance. The rapid discovery and molecular
characterization of novel targets have paved the path for the development of new
antimalarial medicines. To find chemically varied, efficacious medications, new
pharmacophores, and validated targets are necessary. Functional genomics and
structure-based drug design can help in the search for novel potential targets and
therapeutic candidates. Once the putative targets are validated, which are capable of
providing effective and safe drugs, they can be used for screening compounds to
discover new leads, which, successively, can be utilized in the lead optimization
process. Combinatorial chemistry, along with as well as high throughput screening
technologies, is used to generate huge numbers of structurally diverse compounds. This
chapter discusses possible chemotherapeutic targets for antimalarial therapy and their
locations inside the malaria parasite, as well as new lead compounds for rationally
designing new antimalarial medicines.
Keywords: Apicoplast, Aquaporins, CDKs, Medicinal chemistry, NPPs, Plasmodium vivax, Plasmodium falciparum.
