ABSTRACT
Terpenoid indole (TIAs) and β-carboline alkaloids (BCAs), such as suppressant reserpine, vasodilatory yohimbine, and antimalarial quinine, are natural compounds derived from strictosidine. These compounds can exert powerful pharmacological effects but be obtained from limited source in nature. the whole biosynthetic pathway of TIAs and BCAs, The Pictet-Spengler reaction catalyzed by strictosidine synthase (STR; EC: 4.3.3.2) is the rate-limiting step. Therefore, it is necessary to investigate their biosynthesis pathways, especially the role of STR, and related findings will support the biosynthetic generation of natural and unnatural compounds. This review summarizes the latest studies concerning the function of STR in TIA and BCA biosynthesis, and illustrates the compounds derived from strictosidine. The substrate specificity of STR based on its structure is also summarized. Proteins that contain six-bladed four-stranded β-propeller folds in many organisms, other than plants, are listed. The presence of these folds may lead to similar functions among organisms. The expression of STR gene can greatly influence the production of many compounds. STR is mainly applied to product various valuable drugs in plant cell suspension culture and biosynthesis in other carriers.
Subject(s)
Alkaloids/biosynthesis , Carbolines/metabolism , Carbon-Nitrogen Lyases , Indoles/metabolism , Terpenes/metabolismABSTRACT
To explore the mechanism of β-carboline alkaloids inhibiting the migration and invasion of SGC-7901 cells and its correlation with FAK gene expression,CCK-8 method was used to determine the inhibitory rate of β-carboline alkaloids on the proliferation of gastric cancer SGC-7901 cells under different concentrations.The effect of β-carboline alkaloids on the migration and invasion of SGC-7901 cells was used by Transwell compartment.Detection of mRNA and protein expression of FAK genes were used by qRT-PCR and Western blot.Then si-FAK-1051 recombinant plasmid was transfected into SGC-7901 cells.FAK gene silencing effect was identified by qRT-PCR and Western blot technique again.Finally,the effects of FAK gene silencing on proliferation and migration of gastric cancer SGC-7901 cells were detected by CCK-8 kit and Transwell chamber assay respectively.With the increase of the concentration ofβ-carboline alkaloids,the inhibitory rate of SGC-7901 cells in human gastric cancer cells increased gradually,with IC5013.364 mg·L-1.The number of SGC-7901 cells of Transwell compartment in the positive experimental group(5-FU,5 mg·L-1) and the β-carboline alkaloids group decreased significantly(P<0.01) and the number of SGC-7901 cells in the β-carboline alkaloids group was significantly lower than that in the positive experimental group(P<0.01).Compared with the blank control group,the mRNA and protein expression level of FAK genes in the positive experimental group was significantly lower than that in the experimental group of β-carboline alkaloids(P<0.05).After transfection of si-FAK-1051 into gastric cancer SGC-7901 cells,the expression of mRNA and protein of FAK gene was significantly down regulated(P<0.05).SGC-7901 cell proliferation and cell migration ability also decreased significantly(P<0.05).β-carboline alkaloids are more effective than 5-FU in inhibiting migration and invasion of gastric cancer SGC-7901 cells,and the mechanism may be related to the inhibition of mRNA and protein expression of FAK gene by β-carboline alkaloids.
Subject(s)
Humans , Alkaloids , Pharmacology , Carbolines , Pharmacology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Focal Adhesion Kinase 1 , Genetics , Gene Expression Regulation, Neoplastic , Gene Silencing , Neoplasm Invasiveness , Stomach Neoplasms , Drug Therapy , PathologyABSTRACT
Objective To study the alkaloids from leaves of Carthamus tinctorius. Methods The alkaloids were isolated and purified by silica gel, MCI, Sephadex LH-20 column chromatographies, and semi-preparative HPLC, and their structures were elucidated by physical and spectroscopic analysis. Results A new β-carboline alkaloid, 4,9-dimethoxy-1-ethyl-β-carboline (1) along with one known analogue 4-methoxy-1-ethyl-β-carboline (2), were isolated from the leaves of C. tinctorius. Compounds 1 and 2 showed the cytotoxicity against HepG2 cell lines with IC50 values of (15.2 ± 0.58) μmol/L and (17.4 ± 0.33) μmol/L, respectively. Conclusion Compounds 1 and 2 are firstly obtained from Carthamus genus, and compound 1 is a new compound named carthine A. Both compounds 1 and 2 exhibited cytotoxicity against HepG2 cell lines.
ABSTRACT
β-carboline alkaloids are widely distributed in nature. Their structures are usually simple and thus are easy to synthesized or modified. β-carboline alkaloids exhibit a wide range of biological activities, such as antitumor, antimalarial, cure impotence, treatment for type 2 diabetes, antiviral, antifungal, etc. Since its structural features and good biological activities, pharmaceutical corporations and research institutes have focused on it in a long time, which results in β-carboline alkaloids become a research hotspot in organic synthesis and medicinal chemistry areas, especially some pharmaceutical corporations designed and synthesized many β-carboline alkaloids derivatives with excellent biological activities by high throughput screening and computer aided drug design technologies. This review summarizes the recent progress on β-carboline alkaloids extracted from marine organism, terrestrial plant, and fungi together with their biological activities over the past 20 years.