Malaria continues to pose a significant threat to global health, which is exacerbated by the emergence of drug-resistant strains, necessitating the urgent development of new therapeutic options. Due to their substantial bioactivity in treating malaria, pyridine and pyrimidine have become the focal point of drug research. Hybrids of pyridine and pyrimidine offer a novel and promising avenue for developing effective antimalarial agents. The ability of these hybrids to overcome drug resistance is tinted, offering a potential solution to this critical obstacle in the treatment of malaria. By targeting multiple pathways, these hybrid compounds reduce the likelihood of resistance development, providing a promising strategy for combating drug-resistant strains of malaria. The review focuses on the most recent developments in 2018 in the structural optimization of pyridine and pyrimidine hybrid compounds, highlighting modifications that have been shown to improve antimalarial activity. Structure-activity studies have elucidated the essential characteristics required for potency, selectivity, and pharmacokinetics. Molecular docking and virtual screening expedite the identification of novel compounds with enhanced activity profiles. This analysis could aid in developing the most effective pyridine and pyrimidine hybrids as antimalarial agents.
Amongst heterocyclic compounds, quinoline and its derivatives are advantaged scaffolds that appear as a significant assembly motif for developing new drug entities. Aminoquinoline moiety has gained significant attention among researchers in the 21stcentury. Considering the biological and pharmaceutical importance of aminoquinoline derivatives, herein, we review the recent developments (since 2019) in various biological activities of the 4-aminoquinoline scaffold hybridized with diverse heterocyclic moieties such as quinoline, pyridine, pyrimidine, triazine, dioxine, piperazine, pyrazoline, piperidine, imidazole, indole, oxadiazole, carbazole, dioxole, thiazole, benzothiazole, pyrazole, phthalimide, adamantane, benzochromene, and pyridinone. Moreover, by gaining knowledge about SARs, structural insights, and molecular targets, this review may help medicinal chemists design cost-effective, selective, safe, and more potent 4-aminoquinoline hybrids for diverse biological activities.