Molecular Docking, Synthesis, and Tyrosinase Inhibition Activity of Acetophenone Amide: Potential Inhibitor of Melanogenesis

Tyrosinase and its related proteins are responsible for pigmentation disorders, and inhibiting tyrosinase is an established strategy to treat hyperpigmentation. The carbonyl scaffolds can be effective inhibitors of tyrosinase activity, and the fact that both benzoic and cinnamic acids are safe natural substances with such a scaffolded structure, it was speculated that hydroxyl-substituted benzoic and cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. These moieties were incorporated into new chemotypes that displayed in vitro inhibitory effect against mushroom tyrosinase with a view to explore antimelanogenic ingredients. The most active compound, 2-((3-acetylphenyl)amino)-2-oxoethyl(E)-3-(2,4-dihydroxyphenyl)acrylate (5c), inhibited mushroom tyrosinase with an IC50 of 0.0020 ± 0.0002 μ M , while 2-((3-acetylphenyl)amino)-2-oxoethyl 2,4-dihydroxybenzoate (3c) had an IC50 of 27.35 ± 3.6 μ M in comparison to the positive control arbutin and kojic acid with a tyrosinase inhibitory activity of IC50 of 191.17 ± 5.5 μ M and IC50 of 16.69 ± 2.8 μ M , respectively. Analysis of enzyme kinetics revealed that 5c is a competitive and reversible inhibitor with dissociation constant (Ki) value 0.0072 μM. In silico docking studies with mushroom tyrosinase (PDB ID 2Y9X) predicted possible binding modes in the enzymatic pocket for these compounds. The orthohydroxyl of the cinnamic acid moiety of 5c is predicted to form hydrogen bond with the active site side chain carbonyl of Asn 260 (2.16 Å) closer to the catalytic site Cu ions. The acetyl carbonyl is picking up another hydrogen bond with Asn 81 (1.90 Å). The inhibitor 5c passed the panassay interference (PAINS) alerts. This study presents the potential of hydroxyl-substituted benzoic and cinnamic acids and could be beneficial for various cosmetic formulations.

Argentine stingless bee honey: bioactive compounds and health-promoting properties

Despite all the advantages of consuming meliponid honey, meliponiculture has not been sufficiently promoted in Argentina yet, and published studies on these species of bees are very scarce. <i>Tetragonisca fiebrigi</i> honey (<b>TfH</b>) or Yateí honey has recently been incorporated into the Argentine food code. This study assesses antioxidant, anti-inflammatory and analgesic properties and acute toxicity by oral administration of <b>TfH</b> in rats. In addition, we present the melissopalynological analysis and physicochemical characterization. High-performance liquid chromatography identifies and quantifies sugars and phenolic compounds. The <i>T. fiebrigi</i> honey analyzed exhibited ABTS^•+ and DPPH radical scavenging effect (IC₅₀= 98.28 mg/ml and IC₅₀=337.83 mg/ml, respectively). A significant reduction in hind paw edema (44.44%) was observed in rats pretreated with <b>TfH</b> honey (1000 mg/kg b.w.) 3.0 h after dosing and significantly reduced transudative and granuloma weights at all doses tested (27.34%, 35.53% and 47.53% granuloma inhibition). The <b>TfH</b> honey oral administration produced analgesic responses in the three models used (acetic acid, formalin, tail immersion). Ferulic, ellagic, coumaric, gallic, cinnamic acids and the flavonoids quercetin and hesperetin were identified and quantified. Fructose (40.9%), glucose (29.02%) and sucrose (1.06%) were the main sugars. <b>TfH</b> honey administration did not produce lethal effects or clinical signs of disease in the acute toxicity study. The results showed that <i>T. fiebrigi</i> honey could be a good source of bioactive natural compounds with therapeutic and nutritional value.

Quali-Quantitative Study on Phenol Compounds as Early Predictive Markers of Graft Incompatibility: A Case Study on Chestnut (Castanea spp.)

In recent years, research has focused on phenolic compounds and their putative role as markers of graft incompatibility. Thus far, no studies have been conducted on the role of phenolic compounds in chestnut (Castanea spp.). The present study investigated the content of phenolic compounds in different combinations of Castanea spp. cultivars and rootstocks. Analyses were performed on the inner and outer tissues of chestnut grafts at two phenological sampling stages. The separation, identification and quantification of the phenolic markers via HPLC were preceded by an ultrasonic green extraction. Two chromatographic methods were tested for a total of 15 phenol compounds. Flavonol compounds were not detected, while cinnamic acids were found in low concentrations. The amount of gallic acid turned out to be higher at the graft union of the incompatible combination (20.11 ± 1.47 mg/100 gFW vs. 8.94 ± 1.08 mg/100 gFW). The same pattern was observed for catechin (15.79 ± 1.83 mg/100 gFW vs. 9.63 ± 1.98 mg/100 gFW). Differences in tannin concentrations seemed to be species-specific, and were apparently not related to graft incompatibility. The present work underlines the potential application of certain phenol compounds for the early prediction of graft incompatibility in Castanea spp.

Preliminary Observations on Viola calcarata as a Source of Bioactive Compounds: Antioxidant Activity and Phytochemical Profile of Two Alpine Subspecies

Viola L. is a botanical genus with approximately 525 to 620 species, spread worldwide. Several violets are traditionally used as edible flowers and have been recently proved to be a source of bioactive compounds, including flavonols, flavanols, benzoic acids, and cinnamic acids. However, no information is available about the phytochemical profile of the Viola calcarata complex, which is found in the Alpine environment. Thus, the present research aimed to assess the antioxidant activity and the presence of bioactive compounds (anthocyanins and phenolic compounds) in V. calcarata subspecies, to promote their biodiversity and use in the agrifood sector. Two V. calcarata subspecies were chosen, with different colors: V. calcarata subspecies calcarata L., with white (CW), yellow (CY), and violet flowers (CV); and V. calcarata subspecies villarsiana (Roem & Schult.) Merxm., with bicolor (violet and yellow—VB) flowers. CY showed a significantly higher phenolic content (1116.43 mg GAE 100 g−1 FW) than the other subspecies, while CV showed higher values in anthocyanins content (44.73 mg C3G 100 g−1 FW). Regarding the antioxidant activity, CW (215.07 mmol Fe2+ kg−1 FW, 99.53 µmol TE g−1 FW, and 32.30 µmol TE g−1 FW for FRAP, DPPH, and ABTS, respectively) and VB (217.33 mmol Fe2+ kg−1 FW, 90.97 µmol TE g−1 FW, and 29.17 µmol TE g−1 FW for FRAP, DPPH, and ABTS, respectively) showed the highest values. Through HPLC, a total of eight phenolic compounds were quantitatively identified among the two subspecies, including flavonols, cinnamic acids, benzoic acids, catechins, and vitamin C. Though different in their composition, the two subspecies are rich in phenolic compounds, highlighting the importance of preserving their biodiversity and their potential use in the agrifood sector.

Multidrug Resistant Acinetobacter baumannii Biofilms: Evaluation of Phenotypic–Genotypic Association and Susceptibility to Cinnamic and Gallic Acids

Acinetobacter baumannii armed with multidrug resistance (MDR) and biofilm-forming ability is increasingly recognized as an alarming pathogen. A deeper comprehension of the correlation between these two armories is required in circumventing its infections. This study examined the biofilm-forming ability of the isolates by crystal violet staining and the antibiotic susceptibility by broth microdilution method. The genetic basis of the MDR and biofilm-forming phenotypes was screened by polymerase chain reaction. The antimicrobial activities of cinnamic and gallic acids against planktonic cells and biofilms of A. baumannii were investigated, and the findings were confirmed with scanning electron microscopy (SEM). Among 90 A. baumannii isolates, 69 (76.6%) were MDR, and all were biofilm formers; they were classified into weak (12.2%), moderate (53.3%), and strong (34.5%) biofilm formers. Our results underlined a significant association between MDR and enhanced biofilm formation. Genotypically, the presence of blaVIM and blaOXA–23 genes along with biofilm-related genes (ompA, bap, and csuE) was statistically associated with the biofilm-forming abilities. Impressively, both gallic and cinnamic acids could significantly reduce the MDR A. baumannii biofilms with variable degrees dependent on the phenotype–genotype characteristics of the tested isolates. The current findings may possess future therapeutic impact through augmenting antimicrobial arsenal against life-threatening infections with MDR A. baumannii biofilms.

Selected 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors. A look into their use and potential in pre-diabetes and type 2 diabetes

Objectives. This review assesses the comparative safety and efficacy of selected 3-hydroxy-3-methylglutaric acid coenzyme A inhibitors (statins, cinnamic acids. 3-hydroxy-3-methyl glutaric acid) on the pre-onset type 2 diabetes (PT2D) and post-onset type 2 diabetes (T2D)-related cluster of seven features (central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation and inflammation). Methods. Google scholar and PubMed were searched for statin*, flaxseed lignan complex (FLC), cinnamic acid (CA)*, and 3-hydroxy-3-methylglutaric acid (HMGA) in conjunction with each of PT2D, T2D and the cluster of seven. An introduction was followed by findings or absence thereof on the impacts of each of statins, FLC, CAs and HMGA on each member of the cluster of seven. Results. Pravastatin manages three features in PT2D, while a number of the statins improve five in T2D. FLC is negative in PT2D but controls four in T2D; it is not clear if the CAs and HMGA in FLC play a role in this success. CAs have potential in six and HMGA has potential in three of the cluster of seven though yet CAs and HMGA are untested in PT2D and T2D in humans. There are safety concerns with some statins and HMGA but FLC and CAs appear safe in the doses and durations tested. Conclusions. Selected statins, FLC, CAs and HMGA can manage or have a potential to manage at least three features of the cluster of seven. Most of the literature-stated concerns are with select statins but there are concerns (one actual and two potential) with HMGA.