Si-Meng Zhao

New Cytotoxic Naphthohydroquinone Dimers from Rubia alata

Two novel naphthohydroquinone dimers with unprecedented skeletons, rubialatins A (1) and B (2), were isolated from the herbal plant Rubia alata together with their precursor, mollugin (3). The structures were elucidated on the basis of NMR spectra and crystal X-ray diffraction. Compound 1, a racemate, was separated by chiral column chromatography, and the absolute configurations of the enantiomers were determined by the computational methods. Cytotoxicity of 1-3 was evaluated as well as the effect on the NF-κB pathway. Compound (+)-1 showed cytotoxicity and could inhibit NF-κB pathway. Meanwhile, 2 showed cytotoxicity and a synergistic effect with TNF-α on NF-κB activation.

Cytotoxic labdane-type diterpenes from Hedychium longipetalum inhibiting production of nitric oxide.

Three new labdane diterpenes, hedylongnoids A (1), B (2) and C (3), were isolated from the rhizomes of Hedychium longipetalum, together with three known ones yunnancoronarin A (4), hedyforrestin C (5) and hedyforrestin B (6). Their structures were established by spectroscopic analysis, including 2D-NMR spectroscopic techniques. Compounds 1-6 exhibited inhibitory effects against nitric oxide (NO) production in LPS and IFN-γ-induced RAW 264.7 murine macrophages with IC50 values ranging from 0.56 to 7.50 μg/ml, and 3-6 showed cytotoxicities against cancer cell lines SGC-7901 and Hela with IC50 values ranging from 6.21 to 14.53 μg/ml and from 6.58 to 14.83 μg/ml, respectively.

Rubipodanin A, the First Natural N-Desmonomethyl Rubiaceae-Type Cyclopeptide from Rubia podantha, Indicating an Important Role of the N9-Methyl Group in the Conformation and Bioactivity.

One new cyclic hexapeptide named rubipodanin A (1), which is the first identified natural N-desmonomethyl Rubiaceae-type cyclopeptide, together with six known Rubiaceae-type cyclopeptides (2–7) were obtained using the TLC cyclopeptide protosite detection method with ninhydrin from the roots and rhizomes of Rubia podantha. The cyclopeptide structures were elucidated by extensive spectroscopic analysis, including 1D-NMR, 2D-NMR, IR, UV and MS. The solution conformation and biological activities of 1 and RA-V (4) were evaluated, and the results demonstrated that the N 9-methyl group plays a vital role in the maintenance of the conformation and bioactivity.

Natural cyclopeptide RA-V inhibits the NF-κB signaling pathway by targeting TAK1

Rubiaceae-type cyclopeptides (RAs) are a type of plant cyclopeptides from the Rubia that have garnered significant attention owing to their unique bicyclic structures and amazing antitumour activities. Our recent work has shown that RAs suppress inflammation and angiogenesis and induce apoptosis. However, the underlying mechanism and targets remained unknown. Nuclear factor κB (NF-κB) signaling pathway plays a critical role in these biological processes, prompting us to investigate whether and how RAs affect this pathway. By screening compound libraries using NF-κB-dependent luciferase reporter, we observed that RA-V is the best NF-κB inhibitor. Further experiments demonstrated that RA-V interrupted the TAK1–TAB2 interaction and targeted TAK1 in this pathway. Moreover, RA-V prevented endotoxin shock and inhibited NF-κB activation and tumor growth in vivo. These findings clarify the mechanism of RA-V on NF-κB pathway and might account for the majority of known bioactivities of RA-V, which will help RA-V develop as new antiinflammatory and antitumour therapies.

New Labdane diterpenes from Hedychium yunnanense with cytotoxicity and inhibitory effects on nitric oxide production

Abstract Two new labdane diterpenes, hedychenoids A (1) and B (2), were isolated from the rhizomes of Hedychium yunnanense, together with four known ones hedychenone (3), forrestin A (4), villosin (5) and calcaratarin C (6). Their structures were determined on the basis of NMR (1D and 2D) and mass spectroscopic analysis. Compounds 2, 3 and 5 exhibited cytotoxicity against SGC-7901 with IC50 values of 14.88 ± 0.52, 7.08 ± 0.21 and 7.76 ± 0.21 μg/ml, 3 and 5 against HeLa with IC50 values of 9.76 ± 0.48 and 13.24 ± 0.63 μg/ml, respectively. Compounds 2, 5 showed inhibitory effects against nitric oxide production in LPS and IFN-γ-induced RAW 264.7 murine macrophages with IC50 values of 6.57 ± 0.88 and 5.99 ± 1.20 μg/ml, respectively.

A New Sesquiterpene from the Rhizomes of Hedychium yunnanense

A new sesquiterpene, hedyunchene A (1), was isolated from the rhizomes of Hedychium yunnanense, together with two known compounds 6β-hydroxystigmasta-4,22-dien-3-one (2) and 6β-hydroxystigmast-4-en-3-one (3). Their structures were determined on the basis of NMR (1D and 2D) and mass spectroscopic analysis.