Current Topics in Medicinal Chemistry - Volume 22, Issue 28, 2022

Background: Passiflora L. is a genus belonging to the Passifloraceae family, with many species widely used in folk medicine and several pharmacological activities described in the scientific literature, being a major target for the development of new therapeutic products. Studies have identified several bioactive compounds in their composition as responsible for these activities, mainly C-glycoside flavonoids. Objective: The aim of this study was to carry out a review of patents related to the genus and its application in several pharmacological activities, important for the development of new drugs and formulations. Methods: The search was carried out in 5 specialized databases, INPI, EPO, WIPO, Latipat and Derwent, using the term ‘Passiflora’ combined with ‘A61K and A61P', subclasses of section A of the International Patent Classification (IPC), which are destined to medical, dental or hygienic purposes, and therapeutic activity of chemical compounds or medicinal preparation, respectively. Results: 1,198 patents citing the genus in the title or abstract have been found, 508 being duplicates. After exclusion and inclusion criteria, 23 patents written in English, Portuguese and Spanish were selected, which demonstrated biological assays in vivo with species of Passiflora as the only active constituent or incorporated in formulations with other compounds. Conclusion: The findings of this search showed growing interest in research and industrial areas in the pharmaceutical development with species of Passiflora, suggesting that the different bioactive compounds present in the genus can be considered as an important tool for the development of new effective and safe products with pharmacological potential.

With the development of epidermal growth factor receptor (EGFR)-based tyrosine kinase inhibitors (TKIs) and their applications in the clinic, non-small-cell lung cancer (NSCLC) treatment has entered a new era, and a great number of patients have benefited. However, there still exist other subgroups of patients who may not benefit from EGFR TKIs, although EGFR mutation is the main driving mutation that leads to NSCLC. To identify potential NSCLC responders for TKI therapy and to detect EGFR status in vivo, noninvasive technology, such as TKI PET imaging, has been developed in recent years, and a great number of tyrosine kinase-targeted PET tracers have been reported. The visualization and quantification of EGFR expression in vivo by PET would provide the most important information for personalizing NSCLC therapy and prediction of response in clinical. This article reviews the progress of small molecular tyrosine kinase-targeted PET tracers and their applications in preclinical experiments and clinical studies. The current limitations and future development of these tracers are also briefly discussed.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in western societies. Therefore the identification of novel biomarkers to be used as diagnostic or therapeutic targets is of significant scientific interest. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is one such protein shown to be involved in endothelial dysfunction, vascular inflammation and atherogenesis. Several epidemiological studies have associated high Lp-PLA2 activity with an increased risk for CAD even when other CAD risk factors or inflammation markers were included in the multivariate analysis. These findings were strengthened by the results of relevant meta-analyses. However, randomized trials failed to establish Lp-PLA2 as a therapeutic target. Specifically, pharmaceutical inhibition of Lp-PLA2 when compared to the placebo failed to demonstrate a significant association with improved prognosis of patients with stable CAD or after an acute coronary syndrome (ACS). This review focuses on the available data that have investigated the potential role of Lp- PLA2 as a biomarker for CAD.

Atherosclerosis and one of its most serious consequences, coronary artery disease, are important sources of morbidity and mortality globally, necessitating early detection and treatment. Considering their complex pathophysiology, including several harmful processes, a comprehensive approach to diagnosis, prognosis, and therapy is very desirable. Extracellular matrix remodeling is a major component of this dangerous cascade, including the cleavage of constituents (collagen, elastin, proteoglycans) and the propagation or exacerbation of the inflammatory response. Several extracellular matrix degradation indicators have been hypothesized to correlate with the existence, severity, and prognosis of coronary artery disease. The potency of matrix metalloproteinases, notably collagenases and gelatinases, has been the most thoroughly investigated in clinical studies. Stromelysins, matrilysins, transmembrane matrix metalloproteinases, collagen and laminin turnover indicators, as well as fibronectin, have also been studied to a lesser level. Among the most well-studied markers, MMP-1, MMP-2, MMP-8, and MMP-9 have been found increased in patients with cardiovascular risk factors such as metabolic syndrome, its components (obesity, dyslipidemia, diabetes mellitus), and smoking. Increasing concentrations are detected in acute coronary syndromes compared to stable angina pectoris and healthy control groups. It should also be stressed that those extracellular matrix biomarkers may also be detected in high concentrations in other vascular pathologies such as peripheral artery disease, carotid artery disease, aortic aneurysms, and dissections. Despite the advances gained, future research should focus on their importance and, more crucially, their added utility as biomarkers in identifying persons at risk of developing overt coronary artery disease. At the same time, determining the prognosis of coronary artery disease patients using such biomarkers may be important for their adequate care.

Cardiovascular disease is the leading cause of mortality worldwide. Inflammation has long been established as a key component in the pathophysiology of coronary artery disease. The interleukin-1 family consists of 11 members that regulate the inflammatory response through both pro- and anti-inflammatory properties with the Nod-like receptor (NLR) family pyrin domain containing 3 inflammasome having a pivotal role in the process of converting interleukin-1 beta and interleukin- 18, two key inflammatory mediators, into their mature forms. Interleukin-1 affects various cell types that participate in the pathogenesis of atherosclerosis as it enhances the expression of leukocyte adhesion molecules on the surface of endothelial cells and augments the permeability of the endothelial cell barrier, attracting monocytes and macrophages into the vessel wall and aids the migration of smooth muscle cells toward atheroma. It also enhances the aggregation of low-density lipoprotein particles in endothelium and smooth muscle cells and exhibits procoagulant activity by inducing synthesis, cell-surface expression and release of tissue factor in endothelial cells, promoting platelet adhesion. The value of interleukin-1 as a diagnostic biomarker is currently limited, but interleukin-1 beta, interleukin-18 and interleukin-37 have shown promising data regarding their prognostic value in coronary artery disease. Importantly, target anti-inflammatory treatments have shown promising results regarding atherosclerosis progression and cardiovascular events. In this review article, we focus on the immense role of interleukin-1 in atherosclerosis progression, inflammation cascade and in the clinical application of target anti-inflammatory treatments.