Antiproliferative Effects of Alkaloids Isolated from the Tuber of &lt;i&gt;Stephania venosa via&lt;/i&gt; the Induction of Cell Cycle Arrest in Mammalian Cancer Cell Lines

Nantapap Nantapap

doi:10.3844/ajassp.2010.1057.1065

Abstract

Problem statement: S. venosa (Menispermaceae) is used in traditional medicine. The constituents of S. venosa belonging to showed remarkable cytotoxic activity. According to previous research, S. venosa contains several alkaloids, such as protoberberine stephanine cyclanoline and N- methylstepholidine, kamaline, (+)-N-carboxamidostepharine, (-)-O-methylstepharinosine, (-)- stepharinosine, aporphine (-)-O-acethylsukhodiamine and oxostephanosine. The chemical and biological investigations of this plant are interesting to bioassay-guided fractionation, particularly Antiproliferative effects via the induction of cell cycle arrest in mammalian cancer cell lines. Approach: The research was carried out to extract, isolate, purify and elucidate structure of the active compound from the tuber S. venosa. Most of the solvent extracts and isolated compound were evaluated with kinds of mammalian cancer cell lines for investigation on antiproliferative effects. Results: Four alkaloids, tetrahydropalmatine (1), crebanine (2) O-methylbulbocapnine (3) and N- methyltetrahydropalmatine (4) were isolated from the tuber of S. venosa. Charaterization of the compounds were carried out by extensive NMR studies using COSY, HMQC, HMBC and DEPT in addition to other spectroscopic methods. These compounds (1, 2 and 3) were showed evidence of the anticancer activities for cell proliferation inhibition in K562, K562/Adr, GLC4 and GLC4/Adr cell lines due to G0/G1 obstruction by compound 2 and 3 and negligible S phase arrest by compound 1. Conclusion: The result showed slightly increase in S phase by the effect of compound 1, beside the G0/G1 phase was blocked by compound 2 and 3.

Highlights

Stephania genus belong to the Menispermaceae family, comprises of about 45 species and they have been reported 15 species in Thailand (Pharadai et al, 1985)
Several Stephania’s species have been used in traditional medicine to treat a variety of disease (Likhitwitayawuid et al, 1993). This genus is well known as an important source of alkaloids, one of the largest groups of natural products which reveal interesting pharmacological activity (Sugimoto et al, 1988)
We report the isolation, purification and structure elucidation of these four compounds on the basis of extensive spectroscopic analysis (UV, IR, MS, 1H NMR, 13C NMR) as well as by comparison of their spectral data with previously reported values. These compounds are known natural products but this is the first report of the isolation from ethyl acetate and acetone extracts of this plant

Summary

INTRODUCTION

Stephania genus belong to the Menispermaceae family, comprises of about 45 species and they have been reported 15 species in Thailand (Pharadai et al, 1985). Several Stephania’s species have been used in traditional medicine to treat a variety of disease (Likhitwitayawuid et al, 1993) This genus is well known as an important source of alkaloids, one of the largest groups of natural products which reveal interesting pharmacological activity (Sugimoto et al, 1988). We report the isolation, purification and structure elucidation of these four compounds on the basis of extensive spectroscopic analysis (UV, IR, MS, 1H NMR, 13C NMR) as well as by comparison of their spectral data with previously reported values These compounds are known natural products but this is the first report of the isolation from ethyl acetate and acetone extracts of this plant

MATERIALS AND METHODS

Findings

CONCLUSION