Mini Reviews in Medicinal Chemistry - Volume 24, Issue 7, 2024

The glucokinase regulator (GCKR) gene encodes an inhibitor of the glucokinase enzyme (GCK), found only in hepatocytes and responsible for glucose metabolism. A common GCKR coding variation has been linked to various metabolic traits in genome-wide association studies. Rare GCKR polymorphisms influence GKRP activity, expression, and localization. Despite not being the cause, these variations are linked to hypertriglyceridemia. Because of their crystal structures, we now better understand the molecular interactions between GKRP and the GCK. Finally, small molecules that specifically bind to GKRP and decrease blood sugar levels in diabetic models have been identified. GCKR allelic spectrum changes affect lipid and glucose homeostasis. GKRP dysfunction has been linked to a variety of molecular causes, according to functional analysis. Numerous studies have shown that GKRP dysfunction is not the only cause of hypertriglyceridemia, implying that type 2 diabetes could be treated by activating liver-specific GCK via small molecule GKRP inhibition. The review emphasizes current discoveries concerning the characteristic roles of glucokinase and GKRP in hepatic glucose metabolism and diabetes. This information has influenced the growth of directed molecular therapies for diabetes, which has improved our understanding of lipid and glucose physiology.

Tamarixetin and its glycosides are widely distributed in natural plants, and they are also natural flavonoid derivatives of quercetin. Its main pharmacological effects include antioxidant, antiinflammatory, antiviral, anticancer, cardiovascular effects, etc. The pharmacokinetics showed that the distribution of direct absorption differed from that of biosynthesis. At the same time, research shows that tamarixetin is safe to use because it has little self-toxicity. In this paper, 181 articles on tamarixetin published from 1976 to 2023 are obtained from PubMed, China Knowledge Base Database, Wanfang Data, and other electronic databases. Tamarixetin is searched based on keywords, and 121 articles remain. Transformation synthesis, pharmacokinetics, pharmacological action, and structureactivity relationship of tamarixetin were reviewed.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that has traditionally been treated using a variety of pharmacological compounds. However, the effectiveness of these treatments is often limited due to challenges associated with their administration. Oral and parenteral routes of drug delivery are often restricted due to issues such as low bioavailability, rapid metabolism, poor absorption, first-pass effect, and severe side effects. In recent years, nanocarrier-based delivery methods have emerged as a promising alternative for overcoming these challenges. Nanocarriers, including nanoparticles, dendrimers, micelles, nanoemulsions, and stimuli-sensitive carriers, possess unique properties that enable efficient drug delivery and targeted therapy. Using nanocarriers makes it possible to circumvent traditional administration routes' limitations. One of the key advantages of nanocarrier- based delivery is the ability to overcome resistance or intolerance to traditional antirheumatic therapies. Moreover, nanocarriers offer improved drug stability, controlled release kinetics, and enhanced solubility, optimizing the therapeutic effect. They can also protect the encapsulated drug, prolonging its circulation time and facilitating sustained release at the target site. This targeted delivery approach ensures a higher concentration of the therapeutic agent at the site of inflammation, leading to improved therapeutic outcomes. This article explores potential developments in nanotherapeutic regimens for RA while providing a comprehensive summary of current approaches based on novel drug delivery systems. In conclusion, nanocarrier-based drug delivery systems have emerged as a promising solution for improving the treatment of rheumatoid arthritis. Further advancements in nanotechnology hold promise for enhancing the efficacy and safety of RA therapies, offering new hope for patients suffering from this debilitating disease.

Prostate cancer is a disease that is affecting a large population worldwide. Androgen deprivation therapy (ADT) has become a foundation for the treatment of advanced prostate cancer, as used in most clinical settings from neo-adjuvant to metastatic stage. In spite of the success of ADT in managing the disease in the majority of men, hormonal manipulation fails eventually. New molecules are developed for patients with various hormone-refractory diseases. Advancements in molecular oncology have increased understanding of numerous cellular mechanisms which control cell death in the prostate and these insights can lead to the development of more efficacious and tolerable therapies for carcinoma of the prostate. This review is focused on numerous therapies that might be a boon for prostate therapy like signaling inhibitors, vaccines, and inhibitors of androgen receptors. Along with these, various bioactive molecules and their derivatives are highlighted, which act as potential antiprostate cancer agents. This article also emphasized the recent advances in the field of medicinal chemistry of prostate cancer agents.

Background: Phenolic acids have recently gained considerable attention because of their numerous practical, biological, and pharmacological benefits. Various polyphenolic compounds are widely distributed in plant sources. Flavonoids and phenolic acids are the two main polyphenolic compounds that many plants contain abundant polyphenols. Chlorogenic acid, one of the most abundant phenolic acids, has various biological activities, but it is chemically unstable and degrades into other compounds or different enzymatic processes. Methods: In this review, we have studied many publications about CA and its derivatives. CA derivatives were classified into three categories in terms of structure and determined each part’s effects on the body. The biological evaluations, structure-activity relationship, and mechanism of action of CA derivatives were investigated. The search databases for this review were ScienceDirect, Scopus, Pub- Med and google scholar. Results: Many studies have reported that CA derivatives have demonstrated several biological effects, including anti-oxidant, anti-inflammatory, anti-microbes, anti-mutation, anti-carcinogenic, anti-viral, anti-hypercholesterolemia, anti-hypertensive, anti-bacterial, and hypoglycemic actions. The synthesis of new stable CA derivatives can enhance its metabolic stability and biological activity. Conclusion: The present study represented different synthetic methods and biological activities of CA derivatives. These compounds showed high antioxidant activity across a wide range of biological effects. Our goal was to help other researchers design and develop stable analogs of CA for the improvement of its metabolic stability and the promotion of its biological activity.

HDAC9 is a histone deacetylase enzyme belonging to the class IIa of HDACs which catalyses histone deacetylation. HDAC9 inhibit cell proliferation by repairing DNA, arresting the cell cycle, inducing apoptosis, and altering genetic expression. HDAC9 plays a significant part in human physiological system and are involved in various type of diseases like cancer, diabetes, atherosclerosis and CVD, autoimmune response, inflammatory disease, osteoporosis and liver fibrosis. This review discusses the role of HDAC9 in different diseases and structure-activity relationships (SARs) of various hydroxamate and non-hydroxamate-based inhibitors. SAR of compounds containing several scaffolds have been discussed in detail. Moreover, structural requirements regarding the various components of HDAC9 inhibitor (cap group, linker and zinc-binding group) has been highlighted in this review. Though, HDAC9 is a promising target for the treatment of a number of diseases including cancer, a very few research are available. Thus, this review may provide useful information for designing novel HDAC9 inhibitors to fight against different diseases in the future.