Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the development of drug resistance in malaria parasites. The standard treatment for malaria is artemisinin-combination therapy (ACT). Nevertheless, the Plasmodium parasite's extensive resistance to prior drugs and reduced ACT efficiency necessitates novel drug discovery. The progress in discovering novel, affordable, and effective antimalarial agents is significant in combating drug resistance, and the hybrid drug concept can be used to covalently link two or more active pharmacophores that may act on multiple targets. Pyrazole and pyrazoline derivatives are considered pharmacologically necessary active heterocyclic scaffolds that possess almost all types of pharmacological activities. This review summarized recent progress in antimalarial activities of synthesized pyrazole and pyrazoline derivatives. The studies published since 2000 are included in this systematic review. This review is anticipated to be beneficial for future study and new ideas in searching for rational development strategies for more effective pyrazole and pyrazoline derivatives as antimalarial drugs.

Mass-spectrometry-based and X-ray fluorescence-based techniques have allowed the study of the distribution of Zn²⁺ ions at extracellular and intracellular levels over the past few years. However, there are some issues during purification steps, sample preparation, suitability for quantification, and the instruments’ availability. Therefore, work on fluorescent sensors based on 8-aminoquinoline as tools to detect Zn²⁺ ions in environmental and biological applications has been popular. Introducing various carboxamide groups into an 8-aminoquinoline molecule to create 8-amidoquinoline derivatives to improve water solubility and cell membrane permeability is also a recent trend. This review aims to present a general overview of the fluorophore 8-aminoquinoline and its derivatives as Zn²⁺ receptors for zinc sensor probes. Various fluorescent chemosensor designs based on 8-amidoquinoline and their effectiveness and potential as a recognition probe for zinc analysis were discussed. Based on this review, it can be concluded that derivatives of 8-amidoquinoline have vast potential as functional receptors for zinc ions primarily because of their fast reactivity, good selectivity, and bio-compatibility, especially for biological applications. To better understand the Zn²⁺ ion fluorophores’ function, diversity of the coordination complex and geometries need further studies. This review provides information in elucidating, designing, and exploring new 8-amidoquinoline derivatives for future studies for the improvement of chemosensors that are selective and sensitive to Zn²⁺.

Widespread resistance of Plasmodium falciparum to current artemisinin-based combination therapies necessitate the discovery of new medicines. Pharmacophoric hybridization has become an alternative for drug resistance that lowers the risk of drug–drug adverse interactions. In this study, we synthesized a new series of hybrids by covalently linking the scaffolds of pyrano[2,3-c]pyrazole with 4-aminoquinoline via an ethyl linker. All synthesized hybrid molecules were evaluated through in vitro screenings against chloroquine-resistant (K1) and -sensitive (3D7) P. falciparum strains, respectively. Data from in vitro assessments showed that hybrid 4b displayed significant antiplasmodial activities against the 3D7 strain (EC₅₀ = 0.0130 ± 0.0002 μM) and the K1 strain (EC₅₀ = 0.02 ± 0.01 μM), with low cytotoxic effect against Vero mammalian cells. The high selectivity index value on the 3D7 strain (SI > 1000) and the K1 strain (SI > 800) and the low resistance index value from compound 4b suggested that the pharmacological effects of this compound were due to selective inhibition on the 3D7 and K1 strains. Molecular docking analysis also showed that 4b recorded the highest binding energy on P. falciparum lactate dehydrogenase. Thus, P. falciparum lactate dehydrogenase is considered a potential molecular target for the synthesized compound.