Current Topics in Medicinal Chemistry - Volume 23, Issue 27, 2023

Metabolic reprogramming is defined as the skill of cells to change their metabolism to support the induced energy demand due to continuous growth. Metabolic reprogramming is a well- known occurrence in the progression of neoplastic cells, although, evidence has shown that it is present in fibrotic disorders. Post-surgical adhesion as a fibrotic disorder is a medical challenge and is defined by fibrotic bands connected between organs with the abdominal wall. Despite many investigations carried out about the pathogenesis of the disorder but there are many unknowns, therefore, targeting special pathways may have the potential to prevent the formation of fibrotic bands post-operative. Glycolysis is a necessary metabolic pathway in living cells. In hypoxic conditions, it is the dominant pathway in the production of energy for different types of cells such as fibroblasts, immune cells, and endothelial cells. Also, glycolysis is a main downstream target for transforming growth factor β (TGF-β) and upregulates during fibrotic conditions. Furthermore, this is noteworthy that hypoxia induces factor 1 alpha (HIF-1α) as a transcription factor, elevated during the hypoxia condition stimulates different signaling pathways such as TGF-β/SMAD, nuclear factor kappa B (NF-kB), and mTOR pathway to control glycolytic metabolism and T-cell trafficking for immune cell migration. Different evidence has indicated that the administration of glycolytic inhibitors has the potential to prevent the development of fibrotic markers. In this review, we pointed out the role of the glycolysis pathway and its connection to profibrotic cytokines to promote inflammatory and fibrotic pathways. Based on the results of studies related to fibrotic disorders we hypothesized that targeting glycolysis may have therapeutic potential in the prevention of postoperative adhesions.

Depression being a common comorbidity of rheumatoid arthritis (RA) is found to be responsible for the reduction in the lifespan of the sufferer along with the compromised quality of life. The study quoted below highlights the pathogenic pathways, the frequency of RA along with its impact on patients, thus, raising awareness about the concerned topic. It is found that the chances and frequency of developing depression are 2-3 times higher in patients with RA in comparison to the general population. For such studies, self-reported questionnaires along with proper screening of inclusion and exclusion criteria have been employed which helped in a better comparative study of the topic. As per a report from a meta-analysis, 16.8% of patients with RA have been observed to develop severe depression. According to recent research in the related field, the hypothesis of the role of immune-mediated processes and their role in brain networks and inflammation has been found to be engaged in the progression and pathophysiology of depression in patients with RA. Autoimmune mechanisms and cytokines are found to play an essential role in coordination for initiating and sustaining the disorder. Involvement of IL-1, IL-6 and TNF-α has been studied and analysed widely. A number of studies have shown a connection between depression and RA-related physical impairment, fatigue, and increased pain. Higher mortality, reduced treatment compliance, and more comorbidities effects increased suicide risk. It is also found that depression along with RA leads to hospitalizations, which in turn increase the cost of care for the patient. Hence, it could be stated that the study of depression in RA can be an important marker for the progression of RA and its prognosis. The latest treatment strategies for RA include management of symptoms and early disorder treatment The current review aims to investigate and bring the links between RA and its symptoms into the limelight, including the psycho-social, physiological, and neurological aspects along with their molecular mechanism, for a better discernment of the topic for the readers.

Vaccines are instrumental tools to fight against novel and re-emerging pathogens and curb pandemics. Vaccination has been an integral part of the multifaceted public health response to the COVID-19 pandemic. Diverse vaccine platforms have been designed and are currently at different stages of development. Some vaccines are still in early biological testing, while others have been launched after being approved by regulatory agencies worldwide. Genomic vaccines that deliver parts of the viral DNA or RNA to host cells have gained popularity recently due to their high efficiency and fast manufacture. Furthermore, recent clinical studies encouraged the use of different vaccine platforms within the primary vaccination course to enhance the efficacy of vaccination. Herein, we discuss COVID-19 genomic vaccines, which deliver viral genetic material to host cells through diverse biotechnology platforms, including viral vector vaccines, messenger RNA nucleic acid vaccines, and DNA nucleic acid vaccines. We compare and contrast vaccine characteristics, composition, and pros and cons among different genomic vaccine platforms as well as non-genomic vaccines. This review summarizes all current knowledge about COVID-19 genomic vaccines, which could be highly valuable to researchers interested in public health and vaccine development.

A multitude of distinct Mannich bases have been synthesized and evaluated as potential therapeutics for a wide variety of diseases and medical conditions, either in the form of prodrugs or as molecules that trigger a biological response from specific targets. The Mannich reaction has been utilized to enhance the biological activity of numerous compounds, resulting in notable progress in various areas such as anticonvulsant, antimalarial, anticancer, anti-inflammatory, antiproliferative, antibacterial, antimicrobial, antitubercular, antiprotozoal, topoisomerases I and II inhibition, α-glucosidase inhibition, carbonic anhydrase inhibition, as well as research related to anti-Alzheimer's disease and anti-Parkinson's disease. Bioactive semisynthetic Mannich bases derived from natural compounds such as chalcone, curcumin, and thymol have also been identified. Pharmaceutical compounds characterized by low solubility may encounter challenges related to their oral bioavailability, half-life, distribution within tissues, rapid metabolism, toxicity, and various other relevant variables. Mannich bases have the ability to undergo protonation under physiological circumstances, facilitating interactions between ligands and receptors, and enhancing their solubility in water. The experimental findings indicate that the solubility of Mannich base prodrugs is higher compared to that of the parent compound. The use of the multicomponent Mannich reaction has been established as a valuable synthetic methodology for the construction of multifunctional compounds through the application of diverse synthetic strategies under varying reaction conditions. The continuous investigation of synthetic techniques for Mannich reactions involves several approaches, such as employing protocols in aquatic environments, utilizing catalysts that are both biodegradable and reusable, exploring the use of ionic liquids, investigating solvent-free and/or catalyst-free media, and exploring reaction conditions involving microwave and ultrasound irradiation. Consequently, the Mannich reaction has emerged as a powerful technique in the field of medicinal chemistry. It is utilized for the creation of new chemical compounds that possess diverse and attractive biologic features. Additionally, this reaction is employed to alter the physicochemical properties of a potential drug candidate, thereby influencing its bioavailability, efficacy, and pharmacological activity. Due to their favorable bioactivities and synthesis techniques, Mannich bases remain a subject of ongoing attention in the field of medicinal/pharmaceutical chemistry.