To quest new targets of Plasmodium parasite and their potential inhibitors to combat antimalarial drug resistance

• Published in: Journal of parasitic diseases 2024-12, Vol.48 (4), p.671-722
• Main Authors: Biswas, Pratyusa, Roy, Rini, Ghosh, Kuldip, Nath, Debjani, Samadder, Asmita, Nandi, Sisir
• Format: Article
• Language: English
• Subjects: Antimalarial agents; Antiparasitic agents; Blood parasites; Dihydrofolate reductase; Dihydroorotate dehydrogenase; Dihydropteroate synthase; DNA biosynthesis; Drug development; Drug discovery; Drug resistance; Health Promotion and Disease Prevention; Infectious Diseases; Inositol; Kinases; Malaria; Medicine; Medicine & Public Health; Morbidity; Multidrug resistance; Parasite resistance; Parasites; Plasmodium; Protein transport; Proteinase inhibitors; Public health; Review Article; Translation elongation
• ISSN: 0971-7196; 0975-0703
• DOI: 10.1007/s12639-024-01687-x

Malaria remains a global health challenge with significant mortality and morbidity annually, with resistant parasite strains complicating treatment efforts. There is an acute need for novel antimalarial drugs that can put a stop to the future public health crisis caused by the multi-drug resistance strains of the Plasmodium parasite . However, the discovery of these new components is very challenging in the context of the generation of multi-drug resistance properties of malaria. The novel drugs also need to have several properties involving enhanced therapeutic prospects, successful treatment capabilities, and novel mechanisms of action that will forestall the resistance. To successfully achieve this aim researchers are trying to focus on exploring promising malaria targets. Various approaches have been made for the development of drugs for malaria including the remodelling of existing drugs and the development of novel inhibitors which acts on new targets. Advancement in the study provides more information on the biology of parasites and the new targets which help in the development of novel drugs. The present review focuses on the study of novel targets of malaria parasites and subsequent inhibitors of those particular targets. Some of these targets include malarial protease, various transporter proteins, enzymes involved in the synthesis of DNA, and nucleic acids like dihydroorotate dehydrogenase, dihydrofolate reductase, apicoplast and dihydropteroate synthase. Other potential targets are also included in this review such as isoprenoid biosynthesis, farnesyl transferase of parasite, P. falciparum translational elongation factor 2, and phosphatidyl inositol 4 kinase. These promising targets have also been summed up along with their corresponding inhibitors for combating multi-drug resistance malaria.