Mini Reviews in Medicinal Chemistry - Volume 23, Issue 22, 2023

Background: LncRNA not only plays an auxiliary role as an intermediate carrier of genetic information, but also mediates various regulatory functions. The complex and precise regulatory function of lncRNA in development and gene expression has greatly explained the complexity of the genome, and also opened a new avenue for people to understand the complexity of life from the dimension of gene expression. Long non-coding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) is a characterized oncogenic lncRNA in different cancers. This review is dedicated to summarizing the various molecular mechanisms of PCGEM1 and demonstrates that the biological functions exerted by PCGEM1 are good starting points for therapy. Methods: The molecular mechanism of PCGEM1 acting on tumors has been summarized by reviewing the literature available on PubMed. Results: The expression of lncRNA PCGEM1 is abnormally increased in all kinds of tumors, including cervical cancer, prostate cancer, renal carcinoma, gastric cancer, lung cancer, ovarian carcinoma, cough variant asthma, and castration tolerant prostate cancer. Besides, PCGEM1 mediates multiple processes involved in carcinogenesis, including proliferation, invasion, anti-apoptosis, and migration. Conclusion: The potential of PCGEM1 as a therapeutic target for cancer is revealed.

Alzheimer's disease (AD) is the most common form of dementia, having characteristic clinical features of progressive memory loss and visuospatial, language, and cognitive impairment. In addition, patients often suffer from comorbid depression and aggression. Aging is a major contributing factor, though the exact pathophysiological involvement in the disease progression is debatable. Biologists demonstrate that AD is not a result of a single pathological incident. However, an uncontrolled myriad of events is responsible for the pathophysiological condition; hence, it is regarded as a multifaceted disease. Pathophysiologically, AD is described by having a long preclinical stage (proteinopathy accumulation stage), followed by a short prodromal/dementia stage (clinical symptom onset), as evident via biomarker studies. Specific and sensitive biomarkers are needed to track disease progression and treatment. Neuroinflammation is one of the cardinal pathophysiological events of AD that form a positive activation loop between proteinopathy and pro-inflammatory mediators. However, the starting point is inconclusive. The vital cells, like glia, known as brain scavenger cells, remain in harmony between their quiescent and activated morphological states during any stimulus and help to regulate the neuroinflammatory microenvironment. Hence, focusing on the dysfunctional microglia could be a novel therapeutic approach to managing neuroinflammation condition in AD. This review focuses on the translational evidence of anti-diabetic and anti-inflammatory candidates in AD management. It also highlights the importance of the microglia activation spectrum, eicosanoid signaling, cytokine signaling, and inflammatory mediators responsible for the neuroinflammation cascade. The repeated failure of single-approached therapies has diverted researchers’ attention to AD-modifying approaches and AD multimodal treatment plans. This review is an effort to brief the role of new players (like micronutrients and nutraceutical applications) that have been reported as helpful in suppressing AD severity. Apart from anti-diabetic candidates, various insulin-mimetic and insulin-sensitizer drugs have also been assessed to target insulin insensitivity to mitigate AD progression. However, these possibilities are in the investigational stage and not clinically established yet, though various AD animal models have verified the positive outcome.

Neurodegenerative diseases are age-related, multifactorial, and complicated conditions that affect the nervous system. In most cases, these diseases may begin with an accumulation of misfolded proteins rather than decay before they develop clinical symptoms. The progression of these diseases can be influenced by a number of internal and external factors, including oxidative damage, neuro-inflammation, and the accumulation of misfolded amyloid proteins. Astrocytes, with the highest abundance among the cells of the mammalian central nervous system, perform several important activities, such as maintaining brain homeostasis and playing a role in the neurodegenerative condition onset and progress. Therefore, these cells have been considered to be potential targets for managing neurodegeneration. Curcumin, with multiple special properties, has been effectively prescribed to manage various diseases. It has hepato-protective, anti-carcinogenic, cardio-protective, thrombo-suppressive, anti-inflammatory, chemo-therapeutic, anti-arthritic, chemo-preventive, and anti-oxidant activities. In the current review, the effects of curcumin on astrocytes in common neurodegenerative conditions, such as Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease, are discussed. Hence, it can be concluded that astrocytes play a critical role in neurodegenerative diseases, and curcumin is able to directly modulate astrocyte activity in neurodegenerative diseases.

Introduction: Cyclooxygenase (COX), in literature, known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for the formation of prostanoids, including thromboxane and prostaglandins from arachidonic acid. COX-1 does housekeeping activity, whereas COX- 2 induces inflammation. Continuous rise in COX-2 gives birth to chronic pain-associated disorders, i.e., arthritis, cardiovascular complications, macular degeneration, cancer, and neurodegenerative disorders. Despite their potent anti-inflammatory effects, the detrimental effects of COX-2 inhibitors coexist in healthy tissues. Non-preferential NSAIDs cause gastrointestinal discomfort, whereas selective COX-2 inhibitors exert higher cardiovascular risk and renal impairment on chronic use. Methods: This review paper covers key patents published between 2012-2022 on NSAIDs and coxibs, highlighting their importance, mechanism of action, and patents related to formulation and drug combination. So far, several drug combinations with NSAIDS have been used in clinical trials to treat chronic pain besides combating the side effects. Conclusion: Emphasis has been given on the formulation, drug combination, administration routesmodification, and alternative routes, i.e., parenteral, topical, and ocular DEPOT, improving its riskbenefit ratio of NSAIDs to improvise their therapeutic availability and minimize the adverse effects. Considering the wide area of research on COX-2 and ongoing studies, and future scope of view for the better use of the NSAIDs in treating debilitating disease-associated algesia.

Heterocyclic compounds have diverse structure, which makes them broad and economical therapeutic agents. Pyrazole is a five-membered aromatic ring that contains two nitrogen atom and is responsible for the diverse functions of heterocyclic compounds. This implies the need of reviewing the work that already has been done on the potential of pyrazole scaffolds in the field of medicinal chemistry for the synthesis of new compounds with more effective antimicrobial, antioxidant, anticancer, anti-tuberculosis, and anti-inflammatory activities.