Current Medicinal Chemistry - Volume 31, Issue 1, 2024

Heparin, as a glycosaminoglycan, is known for its anticoagulant and antithrombotic properties for several decades. Heparin is a life-saving drug and is widely used for anticoagulation in medical practice. In recent years, there have been extensive studies that heparin plays an important role in non-anticoagulant diseases, such as anti-inflammatory, anti-viral, anti-angiogenesis, anti-neoplastic, anti-metastatic effects, and so on. Clinical observation and in vitro experiments indicate that heparin displays a potential multitarget effect. In this brief review, we will summarize heparin and its derivative's recently studied progress for the treatment of various viral infections. The aim is to maximize the benefits of drugs through medically targeted development, to meet the unmet clinical needs of serious viral diseases.

Obesity is a complex, chronic and inflammatory disease that affects more than one-third of the world’s population, leading to a higher incidence of diabetes, dyslipidemia, metabolic syndrome, cardiovascular diseases, and some types of cancer. Several phytochemicals are used as flavoring and aromatic compounds, also exerting many benefits for public health. This study aims to summarize and scrutinize the beneficial effects of the most important phytochemicals against obesity. Systematic research of the current international literature was carried out in the most accurate scientific databases, e.g., Pubmed, Scopus, Web of Science and Google Scholar, using a set of critical and representative keywords, such as phytochemicals, obesity, metabolism, metabolic syndrome, etc. Several studies unraveled the potential positive effects of phytochemicals such as berberine, carvacrol, curcumin, quercetin, resveratrol, thymol, etc., against obesity and metabolic disorders. Mechanisms of action include inhibition of adipocyte differentiation, browning of the white adipose tissue, inhibition of enzymes such as lipase and amylase, suppression of inflammation, improvement of the gut microbiota, and downregulation of obesity-inducing genes. In conclusion, multiple bioactive compounds-phytochemicals exert many beneficial effects against obesity. Future molecular and clinical studies must be performed to unravel the multiple molecular mechanisms and anti-obesity activities of these naturally occurring bioactive compounds.

Xanthones are widely distributed polyphenols, present commonly in higher plants; Garcinia, Calophyllum, Hypericum, Platonia, Mangifera, Gentiana and Swertia. Xanthone tricyclic scaffold is able to interact with different biological targets, showing antibacterial and cytotoxic effects, as well as potent effects against osteoarthritis, malaria, and cardiovascular diseases. Thus, in this article we focused on pharmacological effects, applications and preclinical studies with the recent updates of xanthon´s isolated compounds from 2017-2020. We found that only α-mangostin, gambogic acid, and mangiferin, have been subjected to preclinical studies with particular emphasis on the development of anticancer, diabetes, antimicrobial and hepatoprotective therapeutics. Molecular docking calculations were performed to predict the binding affinities of xanthone-derived compounds against SARS-CoV-2 M^pro. According to the results, cratoxanthone E and morellic acid demonstrated promising binding affinities towards SARS-CoV-2 M^pro with docking scores of −11.2 and −11.0 kcal/mol, respectively. Binding features manifested the capability of cratoxanthone E and morellic acid to exhibit nine and five hydrogen bonds, respectively, with the key amino acids of the M^pro active site. In conclusion, cratoxanthone E and morellic acid are promising anti-COVID-19 drug candidates that warrant further detailed in vivo experimental estimation and clinical assessment.

Introduction: Physiologically based pharmacokinetic (PBPK) modeling is a computational approach that simulates the anatomical structure of the studied species and presents the organs and tissues as compartments interconnected by arterial and venous blood flows. Aim: The aim of this systematic review was to analyze the published articles focused on the development of PBPK models for interspecies extrapolation in the disposition of drugs and health risk assessment, presenting to this modeling an alternative to reduce the use of animals. Methods: For this purpose, a systematic search was performed in PubMed using the following search terms: “PBPK” and “Interspecies extrapolation”. The revision was performed according to PRISMA guidelines. Results: In the analysis of the articles, it was found that rats and mice are the most commonly used animal models in the PBPK models; however, most of the physiological and physicochemical information used in the reviewed studies were obtained from previous publications. Additionally, most of the PBPK models were developed to extrapolate pharmacokinetic parameters to humans and the main application of the models was for toxicity testing. Conclusion: PBPK modeling is an alternative that allows the integration of in vitro and in silico data as well as parameters reported in the literature to predict the pharmacokinetics of chemical substances, reducing in large quantity the use of animals that are required in traditional studies.