ABSTRACT
Plasmodium parasites are the primary cause of malaria, leading to high mortality rates, which require clinical attention. Many of the medications used in the treatment have resulted in resistance over time. Artemisinin combination therapy (ACT) has shown significant results for the treatment. However, mutations in the parasite have resulted in resistance, leading to decreased efficiency of the medications that are currently being used. Therefore, there is a critical need to find novel scaffolds that are safe, effective, and of economic advantage. Literature has reported several potent molecules with diverse scaffolds designed, synthesized, and evaluated against different strains of Plasmodium. With this growing list of compounds, it is essential to collect the data in one place to gain a concise overview of the emerging scaffolds in recent years. For this purpose, nitrogen-containing heterocycles such as ß-carboline, imidazole, quinazoline, quinoline, thiazole, and thiophene have been highly explored due to their wide biological applications. Besides these, another scaffold, benzodiazepine, which is majorly used as a central nervous system depressant, is emerging as an anti-malarial agent. Hence, this review centers on the latest medication advancements designed to combat malaria, emphasizing special attention to 1,4-benzodiazepines as a novel scaffold for antimalarial drug discovery.
Subject(s)
Antimalarials , Malaria , Antimalarials/pharmacology , Antimalarials/chemistry , Antimalarials/chemical synthesis , Humans , Malaria/drug therapy , Malaria/parasitology , Nitrogen Compounds/chemistry , Nitrogen Compounds/pharmacology , Nitrogen Compounds/chemical synthesis , Plasmodium/drug effects , Animals , Drug Discovery , Drug Resistance , Structure-Activity Relationship , Molecular StructureABSTRACT
Owing to their properties such as biocompatibility, tunable mechanical properties, permeability toward oxygen, nutrients, and the ability to hold a significant amount of water, hydrogels have wide applications in biomedical research. They have been engaged in drug delivery systems, 3D cell culture, imaging, and extracellular matrix (ECM) mimetics. Injectable hydrogels represent a major subset of hydrogels possessing advantages of site-specific conformation with minimal invasive techniques. It preserves the inherent properties of drug/biomolecules and is devoid of any side effects associated with surgery. Various polymeric materials utilized in developing injectable hydrogels are associated with the limitations of toxicity, immunogenicity, tedious manufacturing processes, and lack of easy synthetic tunability. Peptides are an important class of biomaterials that have interesting properties such as biocompatibility, stimuli responsiveness, shear thinning, self-healing, and biosignaling. They lack immunogenicity and toxicity. Therefore, numerous peptide-based injectable hydrogels have been explored in the past, and a few of them have reached the market. In recent years, minimalistic dipeptides have shown their ability to form stable hydrogels through cooperative noncovalent interactions. In addition to inherent properties of lengthy peptide-based injectable hydrogels, dipeptides have the unique advantages of low production cost, high synthetic accessibility, and higher stability. Given the instances of expanding significance of injectable peptide hydrogels in biomedical research and an emerging recent trend of dipeptide-based injectable hydrogels, a timely review on dipeptide-based injectable hydrogels shall highlight various aspects of this interesting class of biomaterials. This concise review that focuses on the dipeptide injectable hydrogel may stimulate the current trends of research on this class of biomaterial to translate its significance as interesting products for biomedical applications.