Seventeen new alkaloids (1-17) and 14 known analogues have been isolated from an aqueous extract of the root of Isatis indigotica. The structures and absolute configurations of these compounds were determined by extensive spectroscopic data analysis, including 2D NMR, single-crystal X-ray crystallography using anomalous scattering of Cu Kα radiation, and electronic circular dichroism spectra calculations based on the quantum-mechanical time-dependent density functional theory. Compounds 1, 2, and 3 are the first examples of natural products with unique linkages between a molecule of 2-(4-methoxy-1H-indol-3-yl)acetonitrile and 2-(1H-indol-3-yl)acetonitrile, 2-(4-methoxy-1H-indol-3-yl)acetonitrile, and 4-hydroxyphenylethane, respectively. Compounds (-)-4 and (+)-4 represent the first natural products with the pyrrolo[2,3-b]indolo[5,5a,6-b,a]quinazoline skeleton. Some structural assignments for the new alkaloids suggest that the assignments made for certain previously reported alkaloids require revision. Compounds 1-3 and arvelexin (18) show antiviral activity against the influenza virus A/Hanfang/359/95 (H3N2), with IC(50) values of 3.70-12.35 μM, and 17 inhibits Coxsackie virus B3 replication with an IC(50) of 6.87 μM.

Alkaloids from the Root of Isatis indigotica

Enantiomers of an Indole Alkaloid Containing Unusual Dihydrothiopyran and 1,2,4-Thiadiazole Rings from the Root of Isatis indigotica

Radix isatidis (R. isatidis) (Banlangen) is a traditional Chinese medicine (TCM) famous for its broad antiviral activity. Its clinical medical history spans several thousands of years in China. Many scientists and scholars have conducted systematic research on this herb from its pharmacognosy to pharmaceuticals, especially in China. Through our research and literature reports, we inferred that the antiviral activity of R. isatidis mostly depended on the water-soluble part, including amino acids, IRPS, nucleosides, and sulfur-containing alkaloids. By playing a role in directly killing pathogenic viruses or regulating the immune system to enhance anti-virus ability, R. isatidis's biological activities mostly depend on the synergistic effect of its multiple components. This article aims to expand understanding of R. isatidis in the following aspects including medicinal resources, chemical constituents, pharmacological activities, clinical applications, and separation and analytical technologies.

Research progress of Chinese herbal medicine Radix isatidis (banlangen).

Indole alkaloids from the roots of Isatis indigotica and their inhibitory effects on nitric oxide production.

Isatis indigotica (2n = 14) is an important medicinal plant in China. Its dried leaves and roots (called Isatidis Folium and Isatidis Radix, respectively) are broadly used in traditional Chinese medicine for curing diseases caused by bacteria and viruses such as influenza and viral pneumonia. Various classes of compounds isolated from this species have been identified as effective ingredients. Previous studies based on transcriptomes revealed only a few candidate genes for the biosynthesis of these active compounds in this medicinal plant. Here, we report a high-quality chromosome-scale genome assembly of I. indigotica with a total size of 293.88 Mb and scaffold N50 = 36.16 Mb using single-molecule real-time long reads and high-throughput chromosome conformation capture techniques. We annotated 30,323 high-confidence protein-coding genes. Based on homolog searching and functional annotations, we identified many candidate genes involved in the biosynthesis of main active components such as indoles, terpenoids, and phenylpropanoids. In addition, we found that some key enzyme-coding gene families related to the biosynthesis of these components were expanded due to tandem duplications, which likely drove the production of these major active compounds and explained why I. indigotica has excellent antibacterial and antiviral activities. Our results highlighted the importance of genome sequencing in identifying candidate genes for metabolite synthesis in medicinal plants.

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A chromosome-scale genome assembly of Isatis indigotica , an important medicinal plant used in traditional Chinese medicine: An Isatis genome.

A new indole alkaloid 1, together with four known indole alkaloids 2–5, was isolated from the 95% EtOH extract of the traditional Chinese medicinal plant Isatis indigotica. Alkaloids 2–5 were found in the plant for the first time. Their structures were elucidated as 3-hydroxy-3-acetonitrile-4-hydroxy-2-indolone (1), 1-methoxy-3-indoleacetonitrile (2), 3-indoleacetic acid (3), 3-indolealdehyde (4), and 1-methoxy-3indolecarbaldehyde (5) on the basis of spectroscopic data. Their anti-HSV effects in vitro were evaluated by plaque reduction assay.

Indole alkaloids from the roots of Isatis ingigotica and their antiherpes simplex virus type 2 (HSV-2) activity in vitro

Two new ceramides were isolated from the 95% EtOH extract of traditional Chinese medicinal plant Isatis indigotica. Their structures were elucidated as 1-O-β-D-glucopyranosyl-(2S, 3R)-N-(2′-hydroxype-ntacosanoyl)-octadeca-11E-sphingenine (1) and 1-O-β-D-glucopyranosyl-(2S,3R)-N-(2′-hydroxyhe xacosanoyl)-octadeca-11E-sphingenine (2) on the basis of spectroscopic data. Their cytotoxic effects were evaluated by using MTT method.

Isolation, structural determination and cytotoxic activity of two new ceramides from the root of Isatis indigotica

In addition to two ceramides 1-O-β-D-glucopyranosyl-(2S,3R)-N-(2'-hydroxyhexadecanoyl)-octadeca-4E,8Esphingenine (2) and (2S,3S,4R)-N-(2'-hydroxytetracosanoyl)-octadecasphingenine (3), which separated for the first time, a new ceramide 1-O-β-D-glucopyranosyl-(2S,3R)-N-(2'-hydroxyhexacosanoyl)octadecasphingenine (1) was isolated from the traditional Chinese medicinal herb Isatis indigotica. Their cytotoxic effects were evaluated by the MTT method.

A new ceramide from the root of Isatis Indigotica and its cytotoxic activity

From the EtOAC extract of the root of Isatis indigotica, a new trihydroxylated monounsaturated fatty acid ester 1, together with two known fatty acids 2–3 that were separated for the first time, has been isolated. The structure of this new linoleic acid-derived metabolite was established as methyl-8,11,12-trihydroxy-9Zoctadecenoic acid on the basis of spectroscopic data.

Wei-Wei Dong

Papers

Indole alkaloids from the roots of Isatis ingigotica and their antiherpes simplex virus type 2 (HSV-2) activity in vitro

Isolation, structural determination and cytotoxic activity of two new ceramides from the root of Isatis indigotica

A new ceramide from the root of Isatis Indigotica and its cytotoxic activity

A new trihydroxy fatty acid ester from the root of Isatis indigotica