RESUMO
Parkinson's disease (PD) is a devastating neurodegenerative condition that mostly damages dopaminergic neurons in the substantia nigra and impairs human motor function. Males are more likely than females to have PD. There are two main pathways associated with PD: one involves the misfolding of α-synuclein, which causes neurodegeneration, and the other is the catalytic oxidation of dopamine via MAO-B, which produces hydrogen peroxide that can cause mitochondrial damage. Parkin (PRKN), α-synuclein (SNCA), heat shock protein (HSP), and leucine-rich repeat kinase-2 (LRRK2) are some of the target areas for genetic alterations that cause neurodegeneration in Parkinson's disease (PD). Under the impact of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is also important in Parkinson's disease (PD), inhibition of mitochondrial complex 1 results in enhanced ROS generation in neuronal cells. Natural products are still a superior option in the age of synthetic pharmaceuticals because of their lower toxicity and moderate side effects. A promising treatment for PD has been discovered using beta-carboline (also known as " ß-carboline") and indole alkaloids. However, there are not many studies done on this particular topic. In the herbs containing ß-carbolines and indoles, the secondary metabolites and alkaloids, ß-carbolines and indoles, have shown neuroprotective and cognitive-enhancing properties. In this review, we have presented results from 18 years of research on the effects of indole and ß-carboline alkaloids against oxidative stress and MAO inhibition, two key targets in PD. In the SAR analysis, the activity has been correlated with their unique structural characteristics. This study will undoubtedly aid researchers in looking for new PD treatment options.
RESUMO
Erratic cell proliferation is the initial symptom of cancer, which can eventually metastasize to other organs. Before cancer becomes metastatic, its spread is triggered by pro-angiogenic factors including vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), Platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and Platelet Factor (PF4), all of which are part of receptor tyrosine kinase (RTK) family. Receptor tyrosine kinases (RTKs) are cell-surface proteins and aresignaling enzymes that transfer ATP-phosphate to tyrosine residue substrates. Important biological processes like proliferation, differentiation, motility, and cell-cycle regulation are all possessedby these proteins. Unusual RTK expression is typically associated with cell growth abnormalities, which is linked to tumor acquisition, angiogenesis, and cancer progression. In addition to the already available medications, numerous other heterocyclic are being studied for their potential action against a variety of cancers. In the fight against cancer, in particular, these heterocycles have been used for their dynamic core scaffold and their inherent adaptability. In this review article, we have compiled last five years research work including nitrogen containing heterocycles that have targeted RTK. Herein, the SAR and activity of various compounds containing diverse heterocyclic (pyrimidine, indole, pyridine, pyrazole, benzimidazole, and pyrrole) scaffolds are discussed, and they may prove useful in the future for designing new leads against RTKs. Our focus in this manuscript is to comprehensively review the latest research on the biological activity and structural activity relationship of nitrogen compounds as RTK inhibitors. We believe that this may be an important contribution to the field, as it can help guide future research efforts and facilitate the development of more effective cancer therapies.