Synthesis and Antiproliferative Activity of Minor Hops Prenylflavonoids and New Insights on Prenyl Group Cyclization.

Jarosław Popłoński,Eliza Turlej,Sandra Sordon,Joanna Wietrzyk,Ewa Huszcza,Tomasz Tronina,Agnieszka Bartmańska

doi:10.3390/molecules23040776

Abstract

Synthesis of minor prenylflavonoids found in hops and their non-natural derivatives were performed. The antiproliferative activity of the obtained compounds against some human cancer cell lines was investigated. Using xanthohumol isolated from spent hops as a lead compound, a series of minor hop prenylflavonoids and synthetic derivatives were obtained by isomerization, cyclisation, oxidative-cyclisation, oxidation, reduction and demethylation reactions. Three human cancer cell lines—breast (MCF-7), prostate (PC-3) and colon (HT-29)—were used in antiproliferative assays, with cisplatin as a control compound. Five minor hop prenyl flavonoids and nine non-natural derivatives of xanthohumol have been synthetized. Syntheses of xanthohumol K, its dihydro- and tetrahydro-derivatives and 1″,2″,α,β-tetrahydroxanthohumol C were described for the first time. All of the minor hops prenyl flavonoids exhibited strong to moderate antiproliferative activity in vitro. The minor hops flavonoids xanthohumol C and 1″,2″-dihydroxanthohumol K and non-natural 2,3-dehydroisoxanthohumol exhibited the activity comparable to cisplatin. Results described in the article suggest that flavonoids containing chromane- and chromene-like moieties, especially chalcones, are potent antiproliferative agents. The developed new efficient, regioselective cyclisation reaction of the xanthohumol prenyl group to 1″,2″-dihydroxantohumol K may be used in the synthesis of other compounds with the chromane moiety.

Highlights

Flavonoids are a group of secondary plant metabolites and important food constituents with a daily intake of a few hundreds of milligrams and positive effects on human health [1]
Suggested that there were only slight differences among xanthohumol derivatives when comparing their cytotoxic activity against HeLa cells
Because the purpose of our research was to obtain derivatives of xanthohumol (1) with a cyclic prenyl group, we isolated our primary compound 1 from spent hops, which is a rich source and it can be purified in considerable amounts [27]

Summary

Introduction

Flavonoids are a group of secondary plant metabolites and important food constituents with a daily intake of a few hundreds of milligrams and positive effects on human health [1]. Their anticancer activity observed at the initiation, promotion, and progression stages of cancer is considered to be a most promising biological phenomenon [2,3]. The female inflorescences of Humulus lupulus, are a natural source of numerous compounds that exhibit a remarkably broad spectrum of biological activities [7,8,9]. Relate to the synthesis and biological activity [15,17]

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