Antiproliferative Phenanthrenes from Juncus tenuis: Isolation and Diversity-Oriented Semisynthetic Modification.

Annamária Kincses,Nikoletta Szemerédi,Andrea Vasas,Dragica Purger,Csaba Bús,Attila Hunyadi,Norbert Kúsz,Róbert Berkecz,Judit Hohmann,László Bakacsy,Gabriella Spengler

doi:10.3390/molecules25245983

Abstract

The occurrence of phenanthrenes is limited in nature, with such compounds identified only in some plant families. Phenanthrenes were described to have a wide range of pharmacological activities, and numerous research programs have targeted semisynthetic derivatives of the phenanthrene skeleton. The aims of this study were the phytochemical investigation of Juncus tenuis, focusing on the isolation of phenanthrenes, and the preparation of semisynthetic derivatives of the isolated compounds. From the methanolic extract of J. tenuis, three phenanthrenes (juncusol, effusol, and 2,7-dihydroxy-1,8-dimethyl-5-vinyl-9,10-dihydrophenanthrene) were isolated. Juncusol and effusol were transformed by hypervalent iodine(III) reagent, using a diversity-oriented approach. Four racemic semisynthetic compounds possessing an alkyl-substituted p-quinol ring (1–4) were produced. Isolation and purification of the compounds were carried out by different chromatographic techniques, and their structures were elucidated by means of 1D and 2D NMR, and HRMS spectroscopic methods. The isolated secondary metabolites and their semisynthetic analogues were tested on seven human tumor cell lines (A2780, A2780cis, KCR, MCF-7, HeLa, HTB-26, and T47D) and on one normal cell line (MRC-5), using the MTT assay. The effusol derivative 3, substituted with two methoxy groups, showed promising antiproliferative activity on MCF-7, T47D, and A2780 cell lines with IC50 values of 5.8, 7.0, and 8.6 µM, respectively.

Highlights

To date, approximately 500 phenanthrenes from 59 genera of 18 families were isolated
More than one hundred phenanthrenes have been isolated from ten Juncus species (J. acutus, J. atratus, J. compressus, J. effusus, J. gerardii, J. inflexus, J. maritimus, J. roemerianus, J. setchuensis, and J. subulatus) [5,6,7,8]
The extract was dissolved in 50% aqueous MeOH, and solvent–solvent partition was performed with n-hexane and C2 H5 O-1: 62.4 (CH2) Cl2

Summary

Introduction

Approximately 500 phenanthrenes from 59 genera of 18 families were isolated. The major sources of phenanthrenes are Orchidaceae, Juncaceae, Combretaceae, and Dioscoreaceae species [1,2]. The family Juncaceae includes up to 500 species belonging to seven genera (Distichia, Juncus, Luzula, Marsippospermum, Oxychloe, Patosia, and Rostkovia). Phenanthrenes are the main bioactive constituents of the Juncaceae species [4]. More than one hundred phenanthrenes have been isolated from ten Juncus species (J. acutus, J. atratus, J. compressus, J. effusus, J. gerardii, J. inflexus, J. maritimus, J. roemerianus, J. setchuensis, and J. subulatus) [5,6,7,8]. Some Juncus species are extremely rich sources of phenanthrenes; for example, from J. effusus, 58 compounds were reported in previous studies. Since various Juncus phenanthrenes are substituted with a vinyl group, such compounds are considered to be important chemotaxonomic markers of the genus [5,9]

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