Cytotoxic Constituents and Molecular Docking Study of the Active Triterpenoids from Tripleurospermum disciforme (C. A. Mey.) Schultz-Bip

Abstract

Background: Terpenoids are produced by a wide variety of plants, animals and microorganisms, which effectively plays a role in the survival of the organisms by means of functional, defensive and communicational attitudes. Objectives:The main purpose of the present study was isolation and elucidation of the natural terpenoids from the aerial parts of Tripleurospermum disciforme (Compositae/Asteraceae family). Methods: The phytochemical investigation of the dichloromethane extract of T. disciforme was carried out by various chromatographical methods such as column chromatography and thin layer chromatography. The major compounds were purified and their structures were established by using nuclear magnetic resonance and electron impact mass spectroscopic data. Moreover, the cytotoxic ability of the isolated compounds were measured on the human gastric carcinoma (AGS) and the mouse skin fibrosarcoma (WEHI-164) cell lines by using MTT assay. Molecular docking studies of the specialized metabolites were performed with Bcl-2, Bcl-xl, CDK2 accompanied by tubulin proteins using AutoDock Vina. Results: Three triterpenoids including (1) taraxasterol; (2) lupeol; and (3) betulinic acid were isolated and elucidated. Our cytotoxic results exhibited that compound 2 could be considered as an anti-tumor component with an IC50 value of 3.2 µM on WEHI-164 cell lines. Likewise, 3 displayed the potent cytotoxic activity, with an IC50 value of 5.6 µM on AGS cell lines. It is noteworthy to mention that the triterpenes 1 -3, newly reported in T. disciforme impacted on the prevention of tubulin polymerization because of the strong interaction with the vinblastine binding site of tubulin. Conclusions: Our data suggested that the isolated triterpenoides from T. disciforme possess anti-tumor properties, and may be included among the effective natural anti-tumors.

The Genus Tripleurospermum Sch. Bip. (Asteraceae): A Comprehensive Review of Its Ethnobotanical Utilizations, Pharmacology, Phytochemistry, and Toxicity

“…It is worth noting that a study analyzing the chemical composition of T. disciforme [ 55 ] found a relatively small amount of β-esquiphellandrene (0.22%), which deviated from previous data. Another recent study [ 74 ] employed techniques such as NMR, electron impact mass spectroscopy, column chromatography, and thin layer- chromatography (see Figure 2 ) to identify three triterpenoids—taraxasterol, lupeol, and betulinic acid—in the dichloromethane extract of T. disciforme .…”

“…Moreover, the dichloromethane extract of T. disciforme demonstrated antitumor activity against human gastric carcinoma (AGS) and mouse skin fibro sarcoma (WEHI-164) cell lines [ 74 ]. However, T. disciforme did not exhibit cytotoxic effects on Pc12 cells [ 124 ].…”

Phytoconstituents from the Aerial Parts of Salvia dracocephaloides Boiss. and their Biological Activities

“…The in vitro cytotoxic activity of the extracts and purified compounds (1 and 2) were examined against MOLT-4 human lymphoblastic leukemia and MCF-7 human breast adenocarcinoma cell lines, respectively, using 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay [6,17]. MCF-7 cells were obtained from Iranian Biological Resource Center, Tehran, Iran, while MOLT-4 cells were purchased from National Cell Bank of Iran, Pasteur Institute, Tehran, Iran.…”