Cytotoxicity-Guided Isolation of Two New Phenolic Derivatives from Dryopteris fragrans (L.) Schott.

Tong Zhang,Sheng-Xiong Huang,De-Hua Duan,Yi-Hao Zhang,Li Wang,Ying Chang

doi:10.3390/molecules23071652

Abstract

Dryopteris fragrans is a valuable medicinal plant resource with extensive biological activities including anti-cancer, anti-oxidation, and anti-inflammation activities. This work aims to study further the cytotoxic constituents from Dryopteris fragrans. In this work, two new phenolic derivatives known as dryofragone (1) and dryofracoumarin B (2) with six known compounds (3–8) were isolated from the petroleum ether fraction of the methanol extract of the aerial parts of Dryopteris fragrans (L.) Schott by two round cytotoxicity-guided tracking with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and cell counting kit-8 (CCK-8) assay. Their structures were elucidated by the extensive spectroscopic analysis (1H-NMR, 13C-NMR, and two dimensions NMR), chemical derivatization, and comparison with data reported in the literature. All the isolates were evaluated for their cytotoxicity against nine cancer cell lines as well as their in vitro immunomodulatory activity. The results showed that compounds have a modest cytotoxicity toward human HeLa cell line with IC50 value below 30 μM and compounds 4 and 5 may modulate immunity to affect the growth of tumor cells.

Highlights

Dryopteris fragrans (L.) Schott (Figure 1) belonging to the genus Dryopteris is a perennial herb with aroma widely distributed throughout the world and is mostly distributed in the alpine and volcanic regions of Northeast China [1,2]
D. fragrans has been used as folk medicine for treating arthritis and skin diseases such as psoriasis, dermatophytosis, and more [3]
Dryofragin, which is a derivative of phloroglucinol, was found to activate the endogenous pathway of apoptosis by affecting the changes of ROS in mitochondria and inducing changes in mitochondria in breast cancer cell MCF-7 and to cause tumor cell apoptosis by the apoptosis-related protein Bcl-2, Bax, Caspase-9, Caspase-3, and PARP [8]

Summary

Introduction

Dryopteris fragrans (L.) Schott (Figure 1) belonging to the genus Dryopteris is a perennial herb with aroma widely distributed throughout the world and is mostly distributed in the alpine and volcanic regions of Northeast China [1,2]. Previous phytochemical investigations on this plant have led to the identification of terpenoids [4], phloroglucinols [5], glucosides [6], and other phenolic derivatives such as coumarin [3]. D. fragrans was a valuable medicinal plant resource with extensive biological activities including anti-cancer, anti-oxidation, insect repellent, anti-microbial, and anti-inflammation activities [3,4,5,6,7]. Of its various biological effects, the mechanism of anti-cancer effects has been studied most. Dryofragin, which is a derivative of phloroglucinol, was found to activate the endogenous pathway of apoptosis by affecting the changes of ROS in mitochondria and inducing changes in mitochondria in breast cancer cell MCF-7 and to cause tumor cell apoptosis by the apoptosis-related protein Bcl-2, Bax, Caspase-9, Caspase-3, and PARP [8]. It has been reported to be an inhibitor of migration and Molecules 2018, 23, 1652; doi:10.3390/molecules23071652 www.mdpi.com/journal/molecules

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