Mini Reviews in Medicinal Chemistry - Volume 22, Issue 17, 2022

Steroidal saponins, a class of natural products formed by the combination of spirosteranes with sugars, are widely distributed in plants and have various biological activities, such as antitumor, anti-inflammatory, anti-bacterial, anti-Alzheimer's, anti-oxidation, etc. Particularly, extensive research on the antitumor property of steroidal saponins has been conducted. Steroidal sapogenins, the aglycones of steroidal saponins, also have attracted much attention due to a vast range of pharmacological activities similar to steroidal saponins. In the past few years, structural modifications on the aglycones and sugar chains of steroidal saponins have been carried out and some achievements have been made. In this mini-review, the antitumor activity, action mechanisms, and structural modifications, along with the structure-activity relationships of steroidal saponins and their derivatives, are summarized.

Bisphenol A (4,4′-isopropylidenediphenol) is an organic compound commonly used in plastic bottles, packaging containers, beverages, and resin industry. The adverse effects of bisphenol A in various systems of the body have been studied. Autophagy is a lysosomal degradation process that leads to the regeneration of new cells. The role of bisphenol A in autophagy modulation involved in the pathogenesis of diseases is still debatable. A few research studies have shown bisphenol Ainduced adverse effects to be associated with autophagy dysregulation, while a few have shown the activation of autophagy to be mediated by bisphenol A. Such contrasting views make the subject more interesting and debatable. In the present review, we discuss the different steps of autophagy, genes involved, and the effect of autophagy modulation by bisphenol A on different systems of the body. We also discuss the methods for monitoring autophagy and the roles of drugs, such as chloroquine, verteporfin, and rapamycin, in autophagy. A proper understanding of the role of bisphenol A in the modulation of autophagy may be important for future treatment and drug discovery.

Among antiviral drugs, the vast majority targets only one or two related viruses. The conventional model, one virus - one drug, significantly limits therapeutic options. Therefore, in the strategy of controlling viral infections, there is a necessity to develop compounds with pleiotropic effects. Favipiravir (FPV) emerged as a strong candidate to become such a drug. The aim of the study is to present up-to-date information on the role of favipiravir in the treatment of viral respiratory infections. The anti-influenza activity of favipiravir has been confirmed in cell culture experiments, animal models, and clinical trials. Thoroughly different - from the previously registered drugs - mechanism of action suggests that FVP can be used as a countermeasure for the novel or re-emerging influenza virus infections. In recent months, favipiravir has been broadly investigated due to its potential efficacy in the treatment of COVID-19. Based on preclinical and clinical studies and a recently published meta-analysis it seems that favipiravir may be a promising antiviral drug in the treatment of patients with COVID-19. FPV is also effective against other RNA respiratory viruses and may be a candidate for the treatment of serious infections caused by human rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza viruses and hantavirus pulmonary syndrome.

Liver cancer is one of the most common malignant tumors, with limited treatment and 8.2% mortality. Liver cancer is the fourth leading cause of cancer-related deaths, which seriously endangers human life and health. Approximately 70% of liver cancer patients show increased serum Alpha- Fetoprotein (AFP) levels. AFP is the main diagnostic and prognostic indicator of liver cancer. AFP, a key marker of liver cancer, plays a crucial role in regulating the proliferation of tumor cells, apoptosis, and induction of cellular immune escape. High levels of AFP during embryonic development protect the embryos from maternal immune attack. AFP also promotes immune escape of liver cancer cells by inhibiting Tumor-Infiltrating Lymphocytes (TILs), Natural Killer cells (NK), Dendritic Cells (DC), and macrophages; thus, it is also used as a target antigen in immunotherapy for liver cancer. AFP is highly expressed in liver cancer cells. In addition to being used in the diagnosis of liver cancer, it has become a target of immunotherapy for liver cancer as a tumor-associated antigen. In immunotherapy, it was also confirmed that early AFP response was positively correlated with the efficacy of immunotherapy. Early AFP responders had longer PFS and OS than non-responders. At present, the methods of immunotherapy for liver cancer mainly include Adoptive Cell Transfer Therapy (ACT), tumor vaccine therapy, immune checkpoint inhibitors (ICIs) therapy, etc. A large number of studies have shown that AFP mainly plays a role in ACT and liver cancer vaccines. This review presents the research progress of AFP and immunosuppression of liver cancer.

Plant-based drugs have a significant impact on modern therapeutics due to their vast array of pharmacological activities. The integration of herbal plants in the current healthcare system has emerged as a new field of research. It can be used for the identification of novel lead compound candidates for future drug development. Nootkatone is a sesquiterpene derivative and an isolate of grapefruit. Shreds of evidence illustrate that nootkatone targets few molecular mechanisms to exhibit its pharmacological activity and yet needs more exploration. The current review is related to nootkatone, drafted through a literature search using research articles and books from different sources, including Science Direct, Google Scholar, Elsevier, PubMed, and Scopus. It has been reported to possess a wide range of pharmacological activities such as anti-inflammatory, anticancer, antibacterial, hepatoprotective, neuroprotective, and cardioprotective. Although preclinical studies in experimental animal models suggest that nootkatone has therapeutic potential, it is further warranted to evaluate its toxicity and pharmacokinetic parameters before being applied to humans. Hence, in the present review, we have summarized the scientific knowledge on nootkatone with a particular emphasis on its pharmacological properties to encourage researchers for further exploration in preclinical and clinical settings.

Alzheimer's disease (AD) is an intricate neurodegenerative disease with chronic and progressive development whose typical neuropathological features encompass senile plaques and neurofibrillary tangles, respectively formed by the extracellular deposition of amyloid-beta (Aβ) and the intracellular accumulation of hyperphosphorylated tau protein in the brain, particularly in limbic and cortical regions. The pathological changes are considered to be caused by the loss of Aβ and tau protein clearance mechanisms under pathological conditions, which leads to an imbalance between the rates of clearance and production. Consequently, the main strategies for treating AD aim to reduce the production of Aβ and hyperphosphorylated tau protein in the brain, inhibit their accumulation, or accelerate their clearance. Although drugs utilizing these therapeutic strategies have been studied successively, their therapeutic effects have generally been less than ideal. Fortunately, recent advances have been made in clearance strategies for these abnormally expressed proteins, including immunotherapies and nanomedicines targeting Aβ or tau, which could represent an important breakthrough for treating AD. Here, we review recent development of the strategies for the removal of abnormal proteins and provide new ideas and methods for treating AD.

Ferroptosis is a novel form of programmed cell death that occurs due to an increase in iron levels. Ferroptosis is implicated in a number of cardiovascular diseases, including myocardial infarction (MI), reperfusion damage, and heart failure (HF). As cardiomyocyte depletion is the leading cause of patient morbidity and mortality, it is critical to thoroughly comprehend the regulatory mechanisms of ferroptosis activation. In fact, inhibiting cardiac ferroptosis can be a useful therapeutic method for cardiovascular disorders. The iron, lipid, amino acid, and glutathione metabolisms strictly govern the beginning and execution of ferroptosis. Therefore, ferroptosis can be inhibited by iron chelators, free radical-trapping antioxidants, GPX4 (Glutathione Peroxidase 4) activators, and lipid peroxidation (LPO) inhibitors. However, the search for new molecular targets for ferroptosis is becoming increasingly important in cardiovascular disease research. In this review, we address the importance of ferroptosis in various cardiovascular illnesses, provide an update on current information regarding the molecular mechanisms that drive ferroptosis, and discuss the role of ferroptosis inhibitors in cardiovascular disease.

Superoxide dismutase (SOD) is a well-known cellular antioxidant enzyme. However, exogenous SOD cannot be used to protect tissues from oxidative damage due to the low permeability of the cell membrane. Cell-penetrating peptides (CPPs) are a class of short peptides that can cross the cell membrane. Recombinant fusion protein that fuses SOD protein with CPP (CPP-SOD) can cross various tissues and organs as well as the blood-brain barrier. CPP-SODs can relieve severe oxidative damage in various tissues caused by radiation, ischemia, inflammation, and chemotherapy by clearing the reactive oxygen species, reducing the expression of inflammatory factors, and inhibiting NF-ΚB/MAPK signaling pathways. Therefore, the clinical application of CPP-SODs provides new therapeutic strategies for a variety of oxidative stress-related disorders, such as Parkinson’s disease, diabetes, obesity, cardiac fibrosis, and premature aging.

Today, finding natural polymers with desirable properties for use in various industries is one of the critical axes of research in the world. Polysaccharides are a group of natural polymers that have various applications in the pharmaceutical industry. The attachment of monosaccharides forms polysaccharides through glycosidic bonds that are widely found in various sources, including plants. Genus Astragalus belongs to the Fabaceae family. Plants belonging to this genus have different polysaccharides. Astragalus polysaccharides (APS) have attracted a great deal of attention among natural polymers because they are non-toxic, biodegradable, and biocompatible. Currently, APS have great drug potential for curing or treating various diseases. Due to the different biological activities of polysaccharides, including Astragalus, this study has investigated the chemical structure of APS, reporting on the antiviral and anti-inflammatory activities as well as stimulation of cytokine secretion by these polysaccharides. Also, in this study, the pharmaceutical approaches of APS compounds, as a natural, new and inexpensive source, have been discussed as suitable candidates for use in pharmaceutical formulations and preparation of new drugs to control COVID-19 infection