Current Topics in Medicinal Chemistry - Volume 24, Issue 2, 2024

Recent developments in the use of natural product-based molecules as antiparasitic agents for Malaria, leishmaniasis (LE), Chagas disease (CD), and Human African trypanosomiasis (HAT) are reviewed. The role of diverse plants in developing bioactive species is discussed in addition to analyzing the structural diversity of natural products as active agents and the diverse biological applications in CD, HAT, LE, and Malaria. This review focuses on medicinal chemistry, emphasizing the structural characteristics of natural molecules as bioactive agents against parasitic infections caused by Leishmania, Trypanosoma, and Plasmodium parasites.

Alzheimer's disease (AD) is a neurological disease that affects the memory. AD has been attributed to the aggregations of amyloid-β (Aβ) peptides which result in the formation of plaques that block the neuron-transferring process done by the brain memory cells. These plaques are formed upon cleavage of Amyloid Precursor Protein (APP) by Gamma-Secretase (GS). GS protein has around 141 substrates, the important two are APP and Notch. Considering one of the hot spots in AD research, we focused on GS and its relation to AD. Moreover, a lot of research was done on beta-secretase and drugs were developed to target it however, few drugs are established for GS. GS contains four subunits: Presenilin (PS), PEN-2, Nicastrin, and APH-1. The catalytic subunit is PS, which contains the active site for substrate binding, as well as the allosteric and docking sites. Both PEN-2 and APH-1 are regulators for the stability and activity of GS. Nicastrin, helps the substrates bind to the PS. Additionally, the role of the immuno-protein named “IFITM3” and how it affects the immune system and its relation to AD is presented. GS is one of the most studied proteins with many developed candidates as inhibitors (GSI) and modulators (GSM). Examples of GSI are Semagacestat and Avagacestat while GSM includes E2012; which inhibits the cleavage activity of GS. In this report, each of the four subunits of GS is described in detail, along with the interactions between GS and its inhibitors or modulators. In addition, the FDA-approved drugs are enlisted.

Background: Gastric cancer develops as a malignant tumor in the mucosa of the stomach, and spreads through further layers. Early-stage diagnosis of gastric cancer is highly challenging because the patients either exhibit symptoms similar to stomach infections or show no signs at all. Biomarkers are active players in the cancer process by acting as indications of aberrant alterations due to malignancy. Objective: Though there have been significant advancements in the biomarkers and therapeutic targets, there are still insufficient data to fully eradicate the disease in its early phases. Therefore, it is crucial to identify particular biomarkers for detecting and treating stomach cancer. This review aims to provide a thorough overview of data analysis in gastric cancer. Methods: Text mining, network analysis, machine learning (ML), deep learning (DL), and structural bioinformatics approaches have been employed in this study. Results: We have built a huge interaction network in the current study to forecast new biomarkers for gastric cancer. The four putatively unique and potential biomarker genes have been identified via a large association network in this study. Conclusion: The molecular basis of the illness is well understood by computational approaches, which also provide biomarkers for targeted cancer therapy. These putative biomarkers may be useful in the early detection of disease. This study also shows that in H. pylori infection in early-stage gastric cancer, the top 10 hub genes constitute an essential component of the epithelial cell signaling pathways. These genes can further contribute to the future development of effective biomarkers.

Cellular senescence, an eternal condition of cell cycle arrest due to cellular stressors, is a sign of aging. Senescent cells (SCs) build up in tissues as they age, impairing their ability to repair themselves by causing the cell cycle to seize in progenitor cells and producing proinflammatory and the senescence-associated secretory phenotype (SASP) or matrix-degrading molecules. SASP aids in the emergence of several age-related diseases. Genetic studies have shown that removing SCs can delay aging and prolong life. Senolytics are small molecules designed to treat numerous age-related disorders can selectively kill SCs. A detailed discussion on senolytics and their potential as therapeutics to treat neuro-disorder and slow down aging is described herein. Emerging natural products, such as quercetin, dasatinib, fisetin, piperlongumine, and curcumin, have recently been reported to be effective senolytic agents, and some structurally modified analogue of these have also been explored for better selectivity and efficacy in animal models. These showed significant potential in clinical studies and could be developed as senolytic drugs in the future.