Current Drug Targets - Volume 23, Issue 5, 2022

The quinolinic ring, present in several molecules, possesses a great diversity of biological activities. Therefore, this ring is in the structural composition of several candidates of drugs in preclinical and clinical studies; thus, it is necessary to compile these results to facilitate the design of new drugs. For this reason, some of the activities of compounds are selected to examine in this review, such as antimalarial, antimicrobial, anticancer, anti-inflammatory, antidiabetic, anti-rheumatic, and antiviral activities. All publications of scientific articles chosen are dated between 2000 and 2020. In addition to presenting the structures of some natural and synthetic compounds with their activities, we have listed the clinical studies of phases III and IV on antimalarial drugs containing the quinoline nucleus and phase III clinical studies on hydroxychloroquine and chloroquine to assess their possible role in COVID-19. Finally, we have reviewed some of the mechanisms of action, as well as the side effects of some of the quinolinic derivatives.

Cardiometabolic diseases (CMD) have caused a great burden in terms of morbidity and mortality worldwide. The vicious cycle of CMD consists of type II diabetes, hypertension, dyslipidemia, obesity, and atherosclerosis. They have interlinked pathways, interacting and interconnecting with each other. The natural flavonoid chrysin has been shown to possess a broad spectrum of therapeutic activities for human health. Herein, we did an in-depth investigation of the novel mechanisms of chrysin’s cardioprotection against cardiometabolic disorders. Studies have shown that chrysin protects the cardiovascular system by enhancing the intrinsic antioxidative defense system. This antioxidant property enhanced by chrysin protects against several risk factors of cardiometabolic disorders, including atherosclerosis, vascular inflammation and dysfunction, platelet aggregation, hypertension, dyslipidemia, cardiotoxicity, myocardial infarction, injury, and remodeling, diabetes-induced injuries, and obesity. Chrysin also exhibited anti-inflammatory mechanisms through inhibiting pro-inflammatory pathways, including NF-ΚB, MAPK, and PI3k/Akt. Furthermore, chrysin modulated NO, RAS, AGE/RAGE, and PPARs pathways which contributed to the risk factors of cardiometabolic disorders. Taken together, the mechanisms in which chrysin protects against cardiometabolic disorder are more than merely antioxidation and anti-inflammation in the cardiovascular system.

Cancer is now also reflected as a disease of the tumor microenvironment, which is primarily supposed to be a decontrolled genetic and cellular expression disease. Over the past two decades, significant and rapid progress has been made in recognizing the dynamics of the tumor's microenvironment and its contribution to influencing the response to various anti-cancer therapies and drugs. Modulations in the tumor microenvironment and immune checkpoint blockade are interesting in cancer immunotherapy and drug targets. Simultaneously, the immunotherapeutic strategy can be implemented by modulating the immune regulatory pathway; however, the tumor microenvironment plays an essential role in suppressing the antitumor's immunity by its substantial heterogeneity. Hypoxia inducible factor (HIF) is a significant contributor to solid tumor heterogeneity and a key stressor in the tumor microenvironment to drive adaptations to prevent immune surveillance. Checkpoint inhibitors here halt the ability of cancer cells to stop the immune system from activating, and in turn, amplify the body's immune system to help destroy cancer cells. Common checkpoints that these inhibitors affect are the PD-1/PDL1 and CTLA-4 pathways, and important drugs involved are Ipilimumab and Nivolumab mainly, along with other drugs in this group. Targeting the hypoxic tumor microenvironment may provide a novel immunotherapy strategy, break down traditional cancer therapy resistance, and build the framework for personalized precision medicine and cancer drug targets. We hope that this knowledge can provide insight into the therapeutic potential of targeting hypoxia and help develop novel combination approaches of cancer drugs to increase the effectiveness of existing cancer therapies, including immunotherapy.

Dementia is a cluster of brain abnormalities that trigger progressive memory deficits and other cognitive abilities such as skills, language, or executive function. Alzheimer’s disease (AD) is the foremost type of age-associated dementia that involves progressive neurodegeneration accompanied by profound cognitive deficits in advanced stages that severely hamper social or occupational abilities with or without the involvement of any other psychiatric condition. The last two decades witnessed a sharp increase (~123%) in mortality due to AD type dementia, typically owing to a very low disclosure rate (~45%) and hence, the prophylactic, as well as the therapeutic cure of AD, has been a huge challenge. Although understanding of AD pathogenesis has witnessed a remarkable growth (e.g., tauopathy, oxidative stress, lipid transport, glucose uptake, apoptosis, synaptic dysfunction, inflammation, and immune system), still a dearth of an effective therapeutic agent in the management of AD prompts the quest for newer pharmacological targets in the purview of its growing epidemiological status. Most of the current therapeutic strategies focus on modulation of a single target, e.g., inhibition of acetylcholinesterase, glutamate excitotoxicity (memantine), or nootropics (piracetam), even though AD is a multifaceted neurological disorder. There is an impedance urgency to find not only symptomatic but effective disease-modifying therapies. The present review focuses on the risk / protective factors and pathogenic mechanisms involved in AD. In addition to the existing symptomatic therapeutic approach, a diverse array of possible targets linked to pathogenic cascades have been re-investigated to envisage the pharmacotherapeutic strategies in AD.

Background: With the advent of food additives centuries ago, the human race has found ways to improve and maintain the safety of utility, augment the taste, color, texture, nutritional value, and appearance of the food. Since the 19th century, when the science behind food spoilage was discerned, food additives in food preservation have been increasing worldwide and at a fast pace to get along with modern lifestyles. Although food additives are thought to be used to benefit the food market, some of them are found to be associated with several health issues at an alarming rate. Studies are still going on regarding the mechanisms by which food additives affect public health. Therefore, an attempt has been made to find out the remedies by exploiting technologies that may convey new properties of food additives that can only enhance the quality of food without having any systemic side effects. Thus, this review focuses on the applications of nanotechnology in the production of nano-food additives and evaluates its success regarding reduction in the health-related hazards by collaterally maintaining the food nutrient value. Methodology: A thorough literature study was performed using scientific databases, like PubMed, Science Direct, Scopus, and Web of Science, for determining the design of the study, and each article was checked for citation and referred to formulate the present review article. Conclusion: Nanotechnology can be applied in the food processing industry to control the unregulated use of food additives and intervene in the biochemical mechanisms at a cellular and physiological level for ensuring the safety of food products. The prospective of nano-additive of chemical origin could be useful to reduce risks of hazards related to human health that are caused majorly due to the invasion of food contaminants (either intentional or non-intentional) into food, though this area still needs scientific validation. Therefore, this review provides comprehensive knowledge on different facets of food contaminants and also serves as a platform of ideas for encountering health risk problems about the design of improved versions of nano-additives.