Semi-synthesis and in vitro anti-cancer effects evaluation of novel xanthohumol derivatives.

Xanthohumol (Xn) is a chalcone compound isolated from Humulus lupulus Linn., that has various biological activities. In this study, eight Xn derivatives were synthesized by Williamson, Mannich, Reimer-Tiemann, and Schiff base reactions, and evaluated for their in vitro cytotoxic activity against five human cancer cell lines (MDA-MB-231, MCF-7, CNE-2Z, SMMC-7721, and H1975). Among these compounds, 2-((E)-2,4-dihydroxy-5-((E)-3-(4-hydroxyphenyl)acryloyl)-6-methoxy-3-(3- methylbut-2-en-1-yl)benzylidene)hydrazine-1-carboximidamide (8) exhibited the most potent cytotoxic activity against the five cancer cells, with IC50 values ranging from 4.87 to 14.35 µM. Wound-healing and transwell assays showed that compound 8 inhibited the migration and invasion of MDA-MB-231 cells by down-regulation HIF-1α, MMP-2 and MMP-9 protein expression. We further demonstrated that compound 8 induced apoptosis of MDA-MB-231 cells by increasing of Bax/Bcl-2 ratio and down-regulation of Akt protein expression.

Key Enzymes Involved in the Synthesis of Hops Phytochemical Compounds: From Structure, Functions to Applications.

Humulus lupulus L. is an essential source of aroma compounds, hop bitter acids, and xanthohumol derivatives mainly exploited as flavourings in beer brewing and with demonstrated potential for the treatment of certain diseases. To acquire a comprehensive understanding of the biosynthesis of these compounds, the primary enzymes involved in the three major pathways of hops' phytochemical composition are herein critically summarized. Hops' phytochemical components impart bitterness, aroma, and antioxidant activity to beers. The biosynthesis pathways have been extensively studied and enzymes play essential roles in the processes. Here, we introduced the enzymes involved in the biosynthesis of hop bitter acids, monoterpenes and xanthohumol derivatives, including the branched-chain aminotransferase (BCAT), branched-chain keto-acid dehydrogenase (BCKDH), carboxyl CoA ligase (CCL), valerophenone synthase (VPS), prenyltransferase (PT), 1-deoxyxylulose-5-phosphate synthase (DXS), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR), Geranyl diphosphate synthase (GPPS), monoterpene synthase enzymes (MTS), cinnamate 4-hydroxylase (C4H), chalcone synthase (CHS_H1), chalcone isomerase (CHI)-like proteins (CHIL), and O-methyltransferase (OMT1). Furthermore, research advancements of each enzyme in terms of reaction conditions, substrate recognition, enzyme structures, and use in engineered microbes are described in depth. Hence, an extensive review of the key enzymes involved in the phytochemical compounds of hops will provide fundamentals for their applications in beer production.