Methoxy-Substituted Tyramine Derivatives Synthesis,Computational Studies and Tyrosinase Inhibitory Kinetics

Targeting tyrosinase for melanogenesis disorders is an established strategy. Hydroxyl-substituted benzoic and cinnamic acid scaffolds were incorporated into new chemotypes that displayed in vitro inhibitory effects against mushroom and human tyrosinase for the purpose of identifying anti-melanogenic ingredients. The most active compound 2-((4-methoxyphenethyl)amino)-2-oxoethyl (E)-3-(2,4-dihydroxyphenyl) acrylate (Ph9), inhibited mushroom tyrosinase with an IC₅₀ of 0.059 nM, while 2-((4-methoxyphenethyl)amino)-2-oxoethyl cinnamate (Ph6) had an IC₅₀ of 2.1 nM compared to the positive control, kojic acid IC₅₀ 16700 nM. Results of human tyrosinase inhibitory activity in A375 human melanoma cells showed that compound (Ph9) and Ph6 exhibited 94.6% and 92.2% inhibitory activity respectively while the positive control kojic acid showed 72.9% inhibition. Enzyme kinetics reflected a mixed type of inhibition for inhibitor Ph9 (K_i 0.093 nM) and non-competitive inhibition for Ph6 (K_i 2.3 nM) revealed from Lineweaver–Burk plots. In silico docking studies with mushroom tyrosinase (PDB ID:2Y9X) predicted possible binding modes in the catalytic site for these active compounds. Ph9 displayed no PAINS (pan-assay interference compounds) alerts. Our results showed that compound Ph9 is a potential candidate for further development of tyrosinase inhibitors.     

Four Novel Phenanthrene Derivatives with α-Glucosidase Inhibitory Activity from Gastrochilus bellinus

Four new phenanthrene derivatives, gastrobellinols A-D (1–4), were isolated from the methanolic extract of Gastrochilus bellinus (Rchb.f.) Kuntze, along with eleven known phenolic compounds including agrostophyllin (5), agrostophyllidin (6), coniferyl aldehyde (7), 4-hydroxybenzaldehyde (8), agrostophyllone (9), gigantol (10), 4-(methoxylmethyl)phenol (11), syringaldehyde (12), 1-(4′-hydroxybenzyl)-imbricartin (13), 6-methoxycoelonin (14), and imbricatin (15). Their structures were determined by spectroscopic methods. Each isolate was evaluated for α-glucosidase inhibitory activity. Compounds 1, 2, 3, 7, 9, 13, and 15 showed higher activity than the drug acarbose. Gastrobellinol C (3) exhibited the strongest α-glucosidase inhibition with an IC₅₀ value of 45.92 μM. A kinetic study of 3 showed competitive inhibition on the α-glucosidase enzyme. This is the first report on the phytochemical constituents and α-glucosidase inhibitory activity of G. bellinus.     

New 2-arylbenzofurans from the root bark of Artocarpus gomezianus and their α-glucosidase inhibitory activity

Two new 2-arylbenzofurans, namely 13-O-methyllakoochin B (1) and artogomezianin (2), were isolated from the root bark of Artocarpus gomezianus, along with six known compounds (3–8). The structures of new compounds were determined by spectroscopic and chemical methods. All of the isolates were evaluated for their α-glucosidase inhibitory activity. Artogomezianin (2) and lakoochin A (3) exhibited strong α-glucosidase inhibitory activity with IC₅₀ values of 18.25 and 26.19 µM, respectively, as compared with the positive control acarbose.     

Enantiodivergent Synthesis of Benzoquinolizidinones from L-Glutamic Acid

Benzoquinolizidinone systems were synthesized in both enantiomeric forms from L-glutamic acid. The key chiral arylethylglutarimide intermediate was synthesized from dibenzylamino-glutamate and homoveratrylamine. Aldol reaction of the glutarimide afforded a mixture of syn and anti-aldol adducts. Subsequent regioselective hydride reduction of the glutarimide carbonyl followed by N-acyliminium ion cyclization afforded a product with opposite absolute configurations at C3 and C11b. Cope elimination of the dibenzylamino group then converted the two diastereomers into enantiomers.     

A new pimarane from Mitrephora tomentosa

A new diterpenoid named (-)-8beta-hydroxypimar-15-en-18-oic acid was isolated, along with (-)-kaur-16-en-19-oic acid, 13,14-dihydrooropheic acid and beta-sitosterol, from the bark of Mitrephora tomentosa.     

6,7,14,15-Tetrahydro[1,5]diazocino[1,2-a:6,5-a′]diindole. Synthesis of a novel pentacyclic ring system

In search of new lead structures for potent allosteric enhancers of antagonist binding to muscarinic M₂ receptors, the first representative of a novel heterocyclic ring system, 6,7,14,15-tetrahydro[1,5]diazocino[1,2-a:6,5-a′]diindole, has been synthesized. The new pentacyclic ring skeleton is obtained from [3-(2-dibenzylaminoethyl)indol-2-yl]-acetic acid methyl ester in three steps.     

Oxyresveratrol protects against DNA damage induced by photosensitized riboflavin

Riboflavin can be photosensitized to produce reactive oxygen species. In the present study, a DNA damage assay was developed based on the photo reaction of riboflavin. In this test system, oxyresveratrol showed higher DNA protective effect than the well-known antioxidants Trolox and ascorbic acid. The results suggest potential applications for oxyresveratrol as an anti-aging agent and a riboflavin stabilizer.