Mini Reviews in Medicinal Chemistry - Volume 24, Issue 5, 2024

Histone deacetylases (HDACs) are a class of enzymes that are responsible for the removal of acetyl groups from the -N-acetyl lysine of histones, allowing histones to wrap DNA more tightly. HDACs play an essential role in many biological processes, such as gene regulation, transcription, cell proliferation, angiogenesis, migration, differentiation and metastasis, which make it an excellent target for anticancer drug discovery. The search for histone deacetylase inhibitors (HDACis) has been intensified, with numerous HDACis being discovered, and five of them have reached the market. However, currently available HDAC always suffers from several shortcomings, such as limited efficacy, drug resistance, and toxicity. Accordingly, dual-targeting HDACis have attracted much attention from academia to industry, and great advances have been achieved in this area. In this review, we summarize the progress on inhibitors with the capacity to concurrently inhibit tubulin polymerization and HDAC activity and their application in cancer treatment.

Background: Cardiovascular Disease is the leading cause of death in adult and pediatric patients with Chronic Kidney Disease (CKD) and its pathogenesis involves the interaction of multiple pathways. As Inflammatory mechanisms play a critical role in the vascular disease of CKD pediatric patients, there are several biomarkers related to inflammation strongly associated with this comorbidity. Objective: This review provides available evidence on the link between several biomarkers and the pathophysiology of heart disease in patients with CKD. Methods: The data were obtained independently by the authors, who carried out a comprehensive and non-systematic search in PubMed, Cochrane, Scopus, and SciELO databases. The search terms were “Chronic Kidney Disease”, “Cardiovascular Disease”, “Pediatrics”, “Pathophysiology”, “Mineral and Bone Disorder (MBD)”, “Renin Angiotensin System (RAS)”, “Biomarkers”, “BNP”, “NTproBNP”, “CK-MB”, “CXCL6”, “CXCL16”, “Endocan-1 (ESM-1)”, “FABP3”, “FABP4”, h-FABP”, “Oncostatin- M (OSM)”, “Placental Growth Factor (PlGF)” and “Troponin I”. Results: The pathogenesis of CKD-mediated cardiovascular disease is linked to inflammatory biomarkers, which play a critical role in the initiation, maintenance, and progression of cardiovascular disease. There are several biomarkers associated with cardiovascular disease in pediatric patients, including BNP, NTproBNP, CK-MB, CXCL6, CXCL16, Endocan-1 (ESM-1), FABP3, FABP4, Oncostatin- M (OSM), Placental Growth Factor (PlGF), and Troponin I. Conclusion: The pathogenesis of CKD-mediated cardiovascular disease is not completely understood, but it is linked to inflammatory biomarkers. Further studies are required to elucidate the pathophysiological and potential role of these novel biomarkers.

DNA methyltransferase (DNMT) is a conserved family of Cytosine methylases, which plays a crucial role in the regulation of Epigenetics. They have been considered promising therapeutic targets for cancer. Among the DNMT family, mutations in the DNMT3A subtype are particularly important in hematologic malignancies. The development of specific DNMT3A subtype inhibitors to validate the therapeutic potential of DNMT3A in certain diseases is a significant task. In this review, we summarized the small molecule inhibitors of DNMT3A discovered in recent years and their inhibitory activities, and classified them based on their inhibitory mechanisms.

Background: Allium sativum L. (Garlic) is a well-recognized plant of great nutraceutical value with pharmacological evidences. It is full of dietary as well as pharmaceutical properties and has been used in traditional medications for a long time. It is known for good antioxidant, antifungal, antibacterial, anti-diabetic, anti-inflammatory, anticancer, and antiviral effects, along with other therapeutic roles in cardiovascular diseases, anti-atherosclerotic, antihypertensive, anti-thrombotic, blood pressure, bone and skin related problems etc. Objective: Considering the potential of garlic in the treatment of cardiovascular/heart-related diseases, the main objective of this study was to prepare a subject-centric mini-review focusing on its chemistry and pharmacology in heart-related issues. Methods: In order to prepare this mini-review article, an extensive online literature search was performed to find out the most recent studies related to this topic. These studies were briefly reviewed, assessed, and discussed to explore the possible capability of garlic for the cure of cardiovascular problems. Result: Several experiments on mice models, rat models as well as on humans show the effective role of various forms of garlic in cardiovascular or heart-related ailments. After reviewing the available publications on garlic in heart-related issues, authors found that garlic and its sulfur (S)-based organic constituents may have advantageous applications in the treatment of cardiovascular diseases.

Background: This review summarizes data on heterocyclic systems with thiadiazole and thiazole fragments in molecules as promising antimicrobial agents. Introduction: Thiadiazole and thiazole backbones are the most favored and well-known heterocycles, a common and essential feature of various drugs. These scaffolds occupy a central position and are the main structural components of numerous drugs with a wide spectrum of action. These include antimicrobial, antituberculous, anti-inflammatory, analgesic, antiepileptic, antiviral, and anticancer agents. Method: The research is based on bibliosemantic and analytical methods using bibliographic and abstract databases, as well as databases of chemical compounds. Result: This review reports on thiadiazole and thiazole derivatives, which have important pharmacological properties. We are reviewing the structural modifications of various thiadiazole and thiazole derivatives, more specifically, the antimicrobial activity reported over the last years, as we have taken this as our main research area. 80 compounds were illustrated, and various derivatives containing hydrazone bridged thiazole and pyrrole rings, 2-pyridine and 4-pyridine substituted thiazole derivatives, compounds containing di-, tri- and tetrathiazole moieties, spiro-substituted 4- thiazolidinone-imidazoline-pyridines were analyzed. Derivatives of 5-heteroarylidene-2,4- thiazolidinediones, fluoroquinolone-thiadiazole hybrids, and others. Conclusion: 1,3,4-thiadiazoles and thiazoles are valuable resource for researchers engaged in rational drug design and development in this area.

Oxidative stress has been reported to be involved in the onset and development of several diseases, including neurodegenerative and cardiovascular disorders, some types of cancer, and diabetes. Therefore, finding strategies to detoxify free radicals is an active area of research. One of these strategies is the use of natural or synthetic antioxidants. In this context, melatonin (MLT) has been proven to possess most of the required characteristics of an efficient antioxidant. In addition, its protection against oxidative stress continues after being metabolized, since its metabolites also exhibit antioxidant capacity. Based on the appealing properties of MLT and its metabolites, various synthetic analogues have been developed to obtain compounds with higher activity and lower side effects. This review addresses recent studies with MLT and related compounds as potential antioxidants.