Synthesis, in silico modelling, and in vitro biological evaluation of substituted pyrazole derivatives as potential anti-skin cancer, anti-tyrosinase, and antioxidant agents.

Twenty-five azole compounds (P1-P25) were synthesised using regioselective base-metal catalysed and microwave-assisted approaches, fully characterised by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), and infrared spectra (IR) analyses, and evaluated for anticancer, anti-tyrosinase, and anti-oxidant activities in silico and in vitro. P25 exhibited potent anticancer activity against cells of four skin cancer (SC) lines, with selectivity for melanoma (A375, SK-Mel-28) or non-melanoma (A431, SCC-12) SC cells over non-cancerous HaCaT-keratinocytes. Clonogenic, scratch-wound, and immunoblotting assay data were consistent with anti-proliferative results, expression profiling therewith implicating intrinsic and extrinsic apoptosis activation. In a mushroom tyrosinase inhibition assay, P14 was most potent among the compounds (half-maximal inhibitory concentration where 50% of cells are dead, IC50 15.9 µM), with activity greater than arbutin and kojic acid. Also, P6 exhibited noteworthy free radical-scavenging activity. Furthermore, in silico docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) simulations predicted prominent-phenotypic actives to engage diverse cancer/hyperpigmentation-related targets with relatively high affinities. Altogether, promising early-stage hits were identified - some with multiple activities - warranting further hit-to-lead optimisation chemistry with further biological evaluations, towards identifying new skin-cancer and skin-pigmentation renormalising agents.

What Is Authentic Maple Water? A Twelve-Month Shelf-Life Study of the Chemical Composition of Maple Water and Its Biological Activities.

Maple water (maple sap) products are produced from sap tapped directly from maple trees, but there is confusion and lack of industry consensus and consumer knowledge as to what constitutes 'authentic' maple water. With an immense potential for growth in the multi-billion dollar functional beverage market, the market promotion of maple water products hinges on establishing standards of identity (SI), which are currently lacking. Herein, we aim to provide publishable SI and compositional chemistry findings of maple water. The chemical composition (including polyphenols, sugars, amino acids, and organic acids) of a pasteurized maple water was monitored over a 12-month (at 0, 4, 8, and 12 months) shelf-life. Furthermore, LC-MS/MS and molecular networking-based methods were developed to identify the phytochemical profile of a maple water extract (MWX) and to compare it to a previously chemically characterized phenolic-enriched maple syrup extract (MSX). Both MSX and MWX have similar phytochemical profiles and chemical characteristics. In addition, MSX and MWX showed moderate antioxidant capacity (in free radical scavenging and anti-tyrosinase assays) and anti-inflammatory effects (in soluble epoxide hydrolase and cyclooxygenase-2 inhibition assays). Our findings provide critical information on the SI and stability (in chemical composition) of maple water, which will help define, authenticate, and distinguish it from other functional beverages, thereby positioning the maple industry for promotion and growth in this market sector.