Synthesis, bioactivity, pharmacokinetic and biomimetic properties of multi-substituted coumarin derivatives

A series of novel multi-substituted coumarin derivatives were synthesized, spectroscopically characterized, and evaluated for their antioxidant activity, soybean lipoxygenase (LOX) inhibitory ability, their influence on cell viability in immortalized human keratinocytes (HaCaT), and cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549) and human melanoma (A375) cells, in vitro. Coumarin analogues 4a–4f, bearing a hydroxyl group at position 5 of the coumarin scaffold and halogen substituents at the 3-phenyl ring, were the most promising ABTS•+ scavengers. 6,8-Dibromo-3-(4-hydroxyphenyl)-4-methyl-chromen-2-one (4k) and 6-bromo-3-(4,5-diacetyloxyphenyl)-4-methyl-chromen-2-one (3m) exhibited significant lipid peroxidation inhibitory activity (IC50 36.9 and 37.1 µM). In the DCF-DA assay, the 4′-fluoro-substituted compound 3f (100%), and the 6-bromo substituted compounds 3i (80.9%) and 4i (100%) presented the highest activity. The 3′-fluoro-substituted coumarins 3e and 4e, along with 3-(4-acetyloxyphenyl)-6,8-dibromo-4-methyl-chromen-2-one (3k), were the most potent lipoxygenase (LOX) inhibitors (IC50 11.4, 4.1, and 8.7 µM, respectively) while displaying remarkable hydroxyl radical scavenging ability, 85.2%, 100%, and 92.9%, respectively. in silico docking studies of compounds 4e and 3k, revealed that they present allosteric interactions with the enzyme. The majority of the analogues (100 µM) did not affect the cell viability of HaCaT cells, though several compounds presented over 60% cytotoxicity in A549 or A375 cells. Finally, the human oral absorption (%HOA) and plasma protein binding (%PPB) properties of the synthesized coumarins were also estimated using biomimetic chromatography, and all compounds presented high %HOA (>99%) and %PPB (60–97%) values. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Use of Edible, Medicinal, and Aromatic Plants in Various Health Disorders: A Cross-Sectional Evaluation among Inhabitants in the Area of Thrace, North-Eastern Greece

Background: Medicinal and aromatical plants (MAPs) have been historically used as traditional remedies in many cultures in Europe and globally. The aim of this study was to evaluate the use of MAPs in various health disorders in association to dietary habits and other lifestyle factors among residents in Thrace, NE Greece. Methods: Data were collected through anonymous and voluntary responses to a structured online questionnaire, via convenience (snowball) sampling. Results: The 561 responders (age: 39.7 ± 11.6 y) were mostly female (59.7%), with higher education (69.8%), working as state or private employees (55.4%), and having low/medium income (77.1%). Overall, more than 70% were using MAPs in various symptoms and common health disorders, such as chamomile against common cold and the flu. More than 20 different MAPs were being used in smaller frequencies against various conditions. Key contributing factors to the consumption of MAPs were sex (female over male), employment (employed vs. unemployed), education (higher education vs. lower) and higher Body Mass Index (overweight and obese vs. normal), while consumption of fruit, fish, and vegetables was mainly associated with the use of MAPs as common items of diet and in health disorders. Conclusions: The use of MAPs as part of the diet and as traditional remedy is present in the examined population, while particular choices seem to be affected by sociodemographic and lifestyle factors

Impact of Foods and Dietary Supplements Containing Hydroxycinnamic Acids on Cardiometabolic Biomarkers: A Systematic Review to Explore Inter-Individual Variability

This article belongs to the Special Issue Plant Food, Nutrition and Human HealthPlant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790