Current Medicinal Chemistry - Volume 29, Issue 12, 2022

Background: Multicomponent reactions are one-pot processes for the synthesis of highly functionalized hetero-cyclic and hetero-acyclic compounds, often endowed with biological activity. Objective: Multicomponent reactions are considered green processes with a high atom economy. In addition, they present advantages compared to the classic synthetic methods, such as high efficiency and low waste production. Methods: In these reactions, two or more reagents are combined together in the same flask to yield a product containing almost all the atoms of the starting materials. Results: The scope of this review is to present an overview of the application of multicomponent reactions in the synthesis of compounds endowed with antiviral activity. The syntheses are classified depending on the viral target. Conclusion: Multicomponent reactions can be applied to all the stages of the drug discovery and development process, making them very useful in the search for new agents active against emerging (viral) pathogens.

The new coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can present neurological symptoms and induce neurological complications. The involvement in both the central and peripheral nervous systems in COVID-19 patients has been associated with direct invasion of the virus and the induction of cytokine storm. This review discussed the pathways for the virus invasion into the nervous system and characterized the SARS-CoV-2 induced cytokine storm. In addition, the mechanisms underlying the immune responses and cytokine storm induction after SARS-CoV-2 infection were also discussed. Although some neurological symptoms are mild and disappear after recovery from infection, some severe neurological complications contribute to the mortality of COVID-19 patients. Therefore, the insight into the cause of SARS-CoV-2 induced cytokine storm in context with neurological complications will formulate the novel management of the disease and also further identify new therapeutic targets for COVID-19.

Irritable bowel syndrome (IBS) is a chronic functional bowel disorder, often stress-related, identified by many abdominal symptoms, the most important of which is chronic visceral abdominal pain. Therefore, IBS commonly impairs the quality of life of patients, moreover, it is frequently linked to depressive and anxiety symptoms. The treatment of IBS primarily focuses on symptoms relief. Unfortunately, up to now, no efficacious therapies have been found. Therefore, it would be important to develop new anti- IBS interventions. The aim of this brief review is to summarize the current evidence of nutraceutical supplementation in IBS treatment, with probiotics, prebiotics, synbiotics, butyrate, palmitoylethanolamide and colostrum. Since nutraceutics are over-the-counter products, the review has the purpose to better inform the medicinal chemist and the practitioner about the possible beneficial mechanisms and the many advantages that these therapies offer. All of these compounds present multiple mechanisms of action, such as restoring the physiological microbiota, potentiating gastrointestinal barrier’s function, immunomodulatory, anti-inflammatory and antinociceptive activities. From the literature data, it results that these compounds are not only capable of improving IBS symptomatology, but mainly display an optimal safety and tolerability profile. Although extensive studies must be carried out to reinforce the evidence from the so far limited clinical trials, the supplementation with these compounds may be useful considering the warnings of prescription medicines for special populations of patients, such as elders, youngsters, or patients who need combination therapy. Finally, the nutraceutical approach may improve adherence to treatment, given its better acceptance by the patients compared to pharmacological therapy.

Background: Currently antibiotic resistant pathogenic bacteria are emerging as an important health problem worldwide. The search for new compounds with antibiotic characteristics is the most promising alternative. Bacteriocins are natural compounds that are inhibitory against pathogens, and Bacillus species are the major producers of these compounds, showing antimicrobial activity against clinically important bacteria. These peptides not only have potential in the pharmaceutical industry but also in food and agricultural sectors. Objective: We provide an overview of the recent bacteriocins isolated from different species of Bacillus including their applications and older bacteriocins. Results: In this review, we have revised some works about the improvements carried out in the production of bacteriocins. Conclusion: These applications make bacteriocins very promising compounds that need to study for industrial production.

Antibiotic resistance is currently a world health crisis that urges the development of new antibacterial substances. To this end, natural products, including flavonoids, alkaloids, terpenoids, steroids, peptides and organic acids play a vital role in the development of medicines and thus constitute a rich source in clinical practices, providing an important source of drugs directly or for the screen of lead compounds for new antibiotic development. Because membrane proteins, which comprise more than 60% of the current clinical drug targets, play crucial roles in signal transduction, transport, bacterial pathogenicity and drug resistance, as well as immunogenicity, it is our aim to summarize those natural products with different structures that target bacterial membrane proteins, such as efflux pumps and enzymes, to provide an overview for the development of new antibiotics to deal with antibiotic resistance.

Nanomaterials represent a wide alternative for the treatment of several diseases that affect both human and animal health. The use of these materials consists, mainly, in trying to solve the problem of resistance that pathogenic organisms acquire to conventional drugs. A well-studied example that represents a potential component for biomedical applications is the use of zinc oxide (ZnO) nanoparticles (NPs). Its antimicrobial function is related, especially to the ability to generate/induce ROS that affects the homeostasis of the pathogen in question. Protozoa and helminths that harm human health and the economic performance of animals have already been exposed to this type of nanoparticle. Thus, through this review, our goal is to discuss the state-of-the-art effect of ZnONPs on these parasites.

In recent years, knowledge of cardiac regeneration mechanisms has dramatically expanded. Regeneration can replace lost parts of organs, common among animal species. The heart is commonly considered an organ with terminal development, which has no reparability potential during post-natal life. However, some intrinsic regeneration capacity has been reported for cardiac muscle, which opens novel avenues in cardiovascular disease treatment. Different endogenous mechanisms have been studied for cardiac repairing and regeneration in recent decades. Survival, proliferation, inflammation, angiogenesis, cell-cell communication, cardiomyogenesis, and anti-aging pathways are the most important mechanisms that have been studied in this regard. Several in vitro and animal model studies focused on proliferation induction for cardiac regeneration reported promising results. These studies have mainly focused on promoting proliferation signaling pathways and demonstrated various signaling pathways such as Wnt, PI3K/Akt, IGF- 1, TGF-β, Hippo, and VEGF signaling cardiac regeneration. Therefore, in this review, we intend to discuss the connection between different critical signaling pathways in cardiac repair and regeneration.

Prolyl-specific peptidases or proteases, including Dipeptidyl Peptidase 2, 4, 6, 8, 9, 10, Fibroblast Activation Protein, prolyl endopeptidase, and prolyl carboxypeptidase, belong to the dipeptidyl peptidase family. In human physiology and anatomy, they have homology amino acid sequences and similarities in the structure; however, they have distinct functions and play different roles. Some of them also play important roles in the metabolism of drugs containing endogenous peptides, xenobiotics containing peptides, and exogenous peptides. The major functions of these peptidases in both the metabolism of human health and bioactive peptides are of significant importance in the development of effective inhibitors to control the metabolism of endogenous bioactive peptides. The structural characteristics, distribution of tissue, endogenous substrates, and biological functions were summarized in this review. Furthermore, the xenobiotics metabolism of the dipeptidyl peptidase family is illustrated. All the evidence and information summarized in this review would be very useful for researchers to extend the understanding of the proteins of these families and offer advice and assistance in physiology and pathology studies.

Background: Ezrin, radixin, and moesin (the ERM complex) interact directly with membrane proteins regulating their attachment to actin filaments. ERM protein activation modifies cytoskeleton organization and alters the endothelial barrier function, thus favoring vascular leakage. However, little is known regarding the role of ERM proteins in diabetic retinopathy (DR). Objective: This study aimed to examine whether overexpression of the ERM complex exists in db/db mice and its main regulating factors. Methods: 9 male db/db mice and 9 male db/+ aged 14 weeks were analyzed. ERM proteins were assessed by western blot and by immunohistochemistry. Vascular leakage was determined by the Evans blue method. To assess ERM regulation, HRECs were cultured in a medium containing 5.5 mM D-glucose (mimicking physiological conditions) and 25 mM D-glucose (mimicking hyperglycemia that occurs in diabetic patients). Moreover, treatment with TNF-α, IL-1β, or VEGF was added to a high glucose condition. The expression of ERM proteins was quantified by RT-PCR. Cell permeability was evaluated by measuring movements of FITC-dextran. Results: A significant increase of ERM in diabetic mice in comparison with non-diabetic mice was observed. A high glucose condition alone did not have any effect on ERM expression. However, TNF-α and IL-1β induced a significant increase in ERM proteins. Conclusion: The increase of ERM proteins induced by diabetes could be one of the mechanisms involved in vascular leakage and could be considered as a therapeutic target. Moreover, the upregulation of the ERM complex by diabetes is induced by inflammatory mediators rather than by high glucose itself.