Drug Development Strategies for Malaria: With the Hope for New Antimalarial Drug Discovery—An Update

Abstract

Malaria continued to be a deadly situation for the people of tropical and subtropical countries. Although there has been a marked reduction in new cases as well as mortality and morbidity rates in the last two decades, the reporting of malaria caused 247 million cases and 619000 deaths worldwide in 2021, according to the WHO (2022). The development of drug resistance and declining efficacy against most of the antimalarial drugs/combination in current clinical practice is a big challenge for the scientific community, and in the absence of an effective vaccine, the problem becomes worse. Experts from various research organizations worldwide are continuously working hard to stop this disaster by employing several strategies for the development of new antimalarial drugs/combinations. The current review focuses on the history of antimalarial drug discovery and the advantages, loopholes, and opportunities associated with the common strategies being followed for antimalarial drug development.

Using 5-Nitroimidazole Derivatives against Neglected Tropical Protozoan Diseases: Systematic Review

“…For example, the total molecular weight, cLogP (octanol/water coefficient, solubility estimation), and the number of sp3 atoms (stereochemical complex-ity estimation) were calculated and statistically analyzed (Table S2). The results suggest that 3-nitroimidazopyridines derivatives (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), metronidazole hybridized derivatives , and quinoline-metronidazole derivatives (63a-63m) have high molecular weights compared with other 5-NI derivatives. These kinds of compounds are in the upper recommended limit to be considered "drug-like" compounds, according to the empirical rules proposed by Lipinsky [70].…”

“…Currently, the emergence of resistant malaria strains creates an urgent need to develop new antimalarial drugs, especially against P. falciparum and P. vivax. Interestingly, a viable alternative is to develop novel 5-NI derivatives, which have demonstrated great potential in in vivo and in vitro models [14]. A representative example of this is the mutation in the Pfcrt gene, associated with the chloroquine (CQ) resistance in P. falciparum, which caused a two-to-three-fold increase in malaria-related deaths during the 1980s.…”

“…Currently, the emergence of resistant malaria strains creates an urgent need to develop new antimalarial drugs, especially against P. falciparum and P. vivax. Interestingly, a viable alternative is to develop novel 5-NI derivatives, which have demonstrated great potential in in vivo and in vitro models [14].…”

Therapeutic Potential of Marine-Derived Cyclic Peptides as Antiparasitic Agents

“…Currently, several strategies for developing new antimalarials are being explored [17]. For example, via synthesis, Wani et al [18] obtained a methalocenic analogue of chloroquine, ferroquine, which is in clinical trials for the treatment of uncomplicated malaria [19].…”

“…Natural products with antimalarial activity include various classes of compounds, such as alkaloids [22], terpenes [23], biflavonoids [24], lactones [25], coumarins [26], xanthones [27], quinones [28], and peptides [29,30]. Other strategies include the identification of new targets and the design of selective inhibitors for these targets [17] or the repositioning of drugs [31,32].…”