Antiviral glycosidic bisindole alkaloids from the roots ofIsatis indigotica

Abstract

Seven new glycosidic bisindole alkaloids, isatindigobisindolosides A-G (1-7), were isolated from an aqueous extract of the Isatis indigotica roots. Their structures including absolute configurations were determined by spectroscopic and chemical methods, together with calculations of electronic circular dichroism (ECD) spectra based on the quantum-mechanical time-dependent density functional theory. In the NMR spectra of 1-3, it is found that integration of H-2 and intensity of C-2 are affected not only by a substitution group at C-2 but also by solvents. Influences of the glucopyranosyloxy on the calculated ECD spectra of the glycosidic bisindole alkaloids are discussed. Compounds 2, 5, and 6 showed antiviral activity against both the influenza virus A/Hanfang/359/95 (H3N2) and Coxsackie virus B3 with IC50 values of 8.4-100.0 μM.

Indole alkaloid sulfonic acids from an aqueous extract of Isatis indigotica roots and their antiviral activity

“…This was confirmed by a typical cyano absorption band at 2257 cm —1 in the IR spectrum of 6 , especially by the HMBC correlations from H-1 to C-2, C-3, C-3a, and C-7a; from H 2 -8 to C-2, C-3, C-3a, and C-9, and from OC H 3 to C-4. In addition, as compared with those of the previously isolated analogues from this extract37, 38, 39, 40, 41, 42, 43, 44, 45, the chemical shifts of C-2 ( δ C 139.0, deshielded) and C-3 ( δ C 99.8, shielded) supported location of the sulfonic acid unit. Therefore, the structure of compound 6 was determined as 3-(cyanomethyl)-4-methoxy-1 H -indole-2-sulfonic acid and named isatindosulfonic acid D.…”

“…for C 23 H 23 N 2 O 9 S, 503.1130) and NMR spectroscopic data. As compared with those of the previously isolated chemical constituents from the same extract37, 38, 39, 40, 41, 42, 43, 44, 45, the NMR spectroscopic data of 1 in CD 3 OD (Table 1) indicated the presence of one 2,3-disubstituted 1 H -indole ring, one 1′ H -indol-3′-yl, a β -glucopyranosyl, and an isolated methine. This, together with the molecular formula, indicated that 1 was an uncommon sulfur-containing bis(indolyl)methane β -glucopyranoside37, 40, 41, of which the planar structure was further elucidated by interpretation of 2D NMR spectroscopic data.…”

“…2) proved that 5 had the parent structure of 1 H -indol-3-ylmethylene. The methoxy group was positioned at N -1 on the basis of the deshielded chemical shifts of the methoxy proton and carbon resonances ( δ H 4.07 and δ C 66.2)41, 42. Meanwhile, a sulfonic acid unit must be put at the methylene unit to fulfill the molecular formula and the remaining substitution position in 5 .…”

“…Accordingly, we investigated an aqueous decoction of “ban lan gen” as part of a program to assess the chemical diversity of traditional Chinese medicines and their biological activities16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36. In our previous papers, more than 70 constituents including 40 new alkaloids in free and glycosidic forms and some with antiviral and cell-damage protective activities37, 38, 39, 40, 41, 42, 43, 44, 45 were reported from I. indigotica for the first time. Herein, reported are isolation, structural characterization, and bioactivity assay of six new indole alkaloid sulfonic acids ( 1 – 6 ), together with two analogues previously prepared as synthetic products ( 7 and 8 , Fig.…”

Aromatic compounds from an aqueous extract of “ban lan gen” and their antiviral activities

“…Therefore, an aqueous decoction of “ban lan gen” was investigated as part of our program to systematically study the chemical and biological diversity of several Chinese traditional medicines10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22. From the decoction, 43 new alkaloids and 54 known compounds, including a pair of indole alkaloid enantiomers containing dihydrothiopyran and 1,2,4-thiadiazole rings, a pair of bisindole alkaloid enantiomers, four stereoisomers of 3,5-bis(2-hydroxybut-3-en-1-yl)-1,2,4-thiadiazole, and twelve glycosidic indole alkaloids, as well as their antiviral and/or hepatocyte-protective activities, were characterized23, 24, 25, 26, 27, 28, 29, 30. Continuous investigation on remaining fractions from the decoction resulted in the separation of a pair of unusual new diphenyl glycerol ether enantiomers (−)- 1 and (+)- 1 and two new methyl benzamidobenzoates ( 2 and 3 ) (Fig.…”