Current Medicinal Chemistry - Volume 30, Issue 31, 2023

Cinnamaldehyde (CNM) is a cyclic terpene alcohol found as the major compound of essential oils from some plants of the genus Cinnamomum (Lauraceae). CNM has several reported pharmacological activities, including antimicrobial, antivirulence, antioxidant, and immunomodulatory effects. These properties make CNM an attractive lead molecule for the development of anti-infective agents. In this descriptive review, we discuss the application of CNM in experimental models of microbial infection using invertebrate and vertebrate organisms. CNM (pure or in formulations) has been successfully applied in the treatment of infections caused by a range of bacterial (such as Cronobacter sakazakii, Escherichia coli, Listeria monocytogenes, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Salmonella enterica, Staphylococcus aureus, Streptococcus agalactiae, Vibrio cholerae;) and fungal (such as Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans) pathogens. All these experimental evidence-based findings have promoted the use of cinnamaldehyde as the leading molecule for developing new anti- infective drugs.

Background: G-protein-coupled receptors (GPCRs) are the largest family of membrane receptors and the most intensively studied drug targets. Given the physiological importance of signal transduction by GPCRs and the recent progress in the structure determination of membrane proteins, the development of GPCR antagonists and agonists is expected to continue to be a major area of medicinal chemistry research. Methods: The structure-property relationship illustrates how the modification of the chemical structure influences the absorption, distribution, metabolism, excretion, and other related properties of drug compounds. Understanding the structure-property relationships of clinically approved GPCR-targeted drugs and their analogues could provide useful information on the lead-to-candidate optimization strategies. Results: Among more than 50 GPCR antagonists and agonists approved in the last decade, the structure-property relationships of 17 drugs are compiled from medicinal chemistry literature, in which detailed pharmacokinetic and toxicological properties are disclosed not only for the final drug candidate but also for key analogues generated during the lead optimization campaign. Conclusion: The structure-property relationships hereby summarized demonstrate how in vitro and in vivo properties of the membrane protein-targeted ligands could be effectively optimized, in many cases, without requiring a significant change in the molecular size. This information is expected to provide valuable insights to expedite new GPCR-targeted drug development.

Lipid metabolism is a complex biochemical process that regulates normal cell activity and death. Ferroptosis is a novel mode of programmed cell death different from apoptosis, pyroptosis, and autophagy. Abnormal lipid metabolism may lead to lipid peroxidation and cell rupture death, which are regulated by lipoxygenase (LOX), long-chain acyl-coA synthases, and antioxidant enzymes. Alternatively, Fe²⁺ and Fe³⁺ are required for the activity of LOXs and ferroptosis, and Fe²⁺ can significantly accelerate lipid peroxidation in ferroptosis. Abnormal lipid metabolism is a certain risk factor for cardiovascular disease. In recent years, the important role of ferroptosis in developing cardiovascular disease has been increasingly reported. Reducing lipid accumulation could reduce the occurrence of ferroptosis, thus alleviating cardiovascular disease deterioration. This article reviews the relationship of lipid peroxidation to the general mechanism of ferroptosis and highlights lipid peroxidation as the common point of ferroptosis and cardiovascular disease.

Genome editing arose as a new promising approach for treating numerous intricate ailm ents including cancer. Over the past couple of decades, delivery technologies that have serendipitously been developed using viral vectors are successful to some extent in protein and nucleic acid delivery but their effectiveness still lags due to their efficiency, tissue targeting capabilities, and toxicity which must be further improved. With the infiltration of nanotechnology into every sphere of life, nano-vehicles can be implemented as an ideal modality that can overcome challenges, also can be introspective as new genome editing tools for cancer therapy owing to the safety and efficiency in clinical settings. Such projected substitution can help in developing highly efficacious therapy regimes which are successful in clinical settings. This emerging approach of incorporation of genome editors (CRISPR/Cas) in different nano vehicles and their utility in targeting various aspects of cancer therapy like treatment, diagnostics, modelling has been comprehensively done in this review.

Atherosclerosis is a multifactorial result of complicated pathophysiology. Changes in the expression of polygenes, coupled with environmental and lifestyle factors, trigger a cascade of adverse events involving a variety of cell types, such as vascular endothelial cells, smooth muscle cells, and macrophages. In this review, we summarize the function and therapeutic targets of atherosclerotic cells. This article reviews the role of endothelial cells, smooth muscle cells, macrophages and foam cells in the development of atherosclerosis and the progress in the treatment of atherosclerosis by targeting these cells. Atherosclerotic plaque involves a variety of cells and biomolecules, and its complex biological environment is a difficult point for the study and treatment of atherosclerosis. For treating atherosclerosis, a large number of studies emerged based on blocking or inhibiting factors affecting the formation and development of plaque. Cardiovascular stent intervention is currently the main method for the treatment of atherosclerosis. In recent decades, numerous studies on cardiovascular, stents mainly involve drug coating or biomolecular modification of stents to enhance anti-thrombosis, anti-restenosis and endothelialization. This paper introduces the research status of cardiovascular stents and new strategies for surface modification. The treatment of atherosclerosis based on the level of molecular biology and cell biology is becoming a research hotspot in the coming decades.