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

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.

Dihydrophenanthrenes from a Sicilian Accession of Himantoglossum robertianum (Loisel.) P. Delforge Showed Antioxidant, Antimicrobial, and Antiproliferative Activities

“…These results match those previously reported by other researchers, which highlighted an anti-proliferative activity of phenanthrenes and 9,10-dihydrophenanthrenes on several cancer cell lines derived from different tumor types, such as leukemia, breast, colon, prostate, and lung cancer [10,55]. Notably, several papers reported that similar molecules, at comparable doses, are effective on cancer cells and well tolerated by normal cells, suggesting a possible selective toxicity [56][57][58][59].…”

Development and Validation of Quantitative Analysis Method for Phenanthrenes in Peels of the Dioscorea Genus

“…Phenanthrenes that have been isolated so far can be classified into three major groups by differences in their substitutents, which include monophenanthrenes, diphenanthrenes, and triphenanthrenes [ 3 ]. As of today, various biological activities of phenanthrenes have been reported, such as antimicrobial [ 3 ], antioxidant [ 4 ], anticancer [ 5 ], antiproliferative [ 6 ], anti-inflammatory [ 7 ], and antiallergic [ 8 ], and spasmolytic effects [ 3 ]. Moreover, phenanthrenes have been suggested to be a non-polar standard marker for genus Dioscorea [ 4 ].…”