ABSTRACT
Herein, we report an extensive phytochemical study on the whole plant of Drymaria cordata, which led to the isolation of ten new orbitides, named drymariamides A-J (1-10). Compounds 2, 3, and 5 incorporate rare residues of noncanonical amino acids of kynurenine (Kyn) or 3a-hydroxypyrroloindoline (HPI). Their structures with absolute configurations were elucidated by a combination of spectroscopic analysis, advanced Marfey's method, X-ray diffraction, and electronic circular dichroism analysis. Compounds 1-10 exhibited antiadipogenic effects in 3T3-L1 adipocytes, and the most potent compound 7 showed an EC50 value of 1.17 ± 0.19 µM.
Subject(s)
3T3-L1 Cells , Amino Acids , Peptides, Cyclic , Animals , Mice , Amino Acids/chemistry , Molecular Structure , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Adipogenesis/drug effects , Adipocytes/drug effects , Adipocytes/metabolismABSTRACT
Croton laui (Euphorbiaceae) is a traditional medicinal plant used by the Li ethnic group in China to treat headaches, stomachaches, and diphtheria. To understand the pharmacological basis of its medicinal use, an extensive investigation of the ethanolic extract of the bark of C. laui was performed. After repeated chromatography, twenty-four undescribed labdane-type diterpenoids, lauinoids A-X (1-24), and five known analogs (25-29) were isolated. Their structures and absolute configurations were established using a combination of spectroscopic analyses, electronic circular dichroism, nuclear magnetic resonance calculations, and single-crystal X-ray diffraction. Among them, compounds 1-3 exhibited an 11(12 â 13)-abeo-16-nor-labdane skeleton, which originated putatively from 9 through a plausible pathway that involves a semipinacol rearrangement process. Compounds 11 and 12 belong to the rare class of 14,15-dinor-labdane diterpenoids. Compounds 18 and 28 exhibited substantial inhibitory effects by suppressing lipopolysaccharide-induced NO production in RAW 264.7 macrophages, with IC50 values of 3.37 ± 0.23 and 5.82 ± 0.28 µM, respectively. This study has greatly expanded the chemical diversity of labdane diterpenoids from C. laui and will guide future research on this ethnomedicinal plant.
Subject(s)
Anti-Inflammatory Agents , Croton , Diterpenes , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/isolation & purification , Croton/chemistry , Mice , Animals , RAW 264.7 Cells , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Lipopolysaccharides/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Molecular Structure , Structure-Activity Relationship , Nitric Oxide/biosynthesis , Nitric Oxide/antagonists & inhibitors , Molecular Conformation , Dose-Response Relationship, DrugABSTRACT
Eleven previously uncharacterized steroids, along with three analogs were isolated from Aglaia lawii leaves. Their structures were definitely characterized by the methods of NMR, MS, IR, ECD and X-ray crystallography study. Among these unreported compounds, 3-epi-dyscusin C, 3-epi-lansisterone E and (Z)-2α-hydroxyaglawone were C-21 pregnane steroids incorporating a highly oxygenated ring A, while others were Δ5-3ß-hydroxy-7-ketosteroids bearing different ring D and C-17 aliphatic chains. All isolates were evaluated for nitric oxide (NO) inhibitory activities. 3-Epi-dyscusin C, 3-epi-lansisterone E, (Z)-2α-hydroxyaglawone and 17(20)E-dyscusin B showed significant anti-inflammatory activities with IC50 values of NO inhibition less than 10 µM (in the range from 4.47 ± 0.36 to 7.67 ± 0.46 µM).
Subject(s)
Aglaia , Molecular Structure , Nitric Oxide , Plant Leaves , Pregnanes/pharmacology , Steroids/pharmacologyABSTRACT
Four previously undescribed steroids, identified as (3S,7S,8S,9S,10R,13S,14S,16S,17R,20S)-7α-methoxy-ergosta-5,24(28)-dien-3ß,16ß,20-triol (1), ergosta-5,24(28)-dien-3ß,7α,16ß-triol (2), ergosta-5,25-dien-3ß,7α,16ß,20-tetrol (3) and 7α,16ß,24α-trihydroxy-varninasterol (4), as well as five known analogues (5-9), were isolated from the leaves and twigs of Dysoxylum pallens Hiern (Meliaceae). Their structures were elucidated based on extensive spectroscopic analysis such as HR-ESI-MS, 1D and 2D NMR, UV, and IR. The absolute configuration of compound 1 was determined by X-ray diffraction analysis. Selected compounds were evaluated for their cytotoxic activities. Compounds 1, 2, and 8 exhibited moderate cytotoxic activity against HL-60, Hela, and HepG2 tumor cell lines with IC50 ranged from 11.09 to 17.51 µM.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Meliaceae/chemistry , Steroids/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , China , HL-60 Cells , HeLa Cells , Hep G2 Cells , Humans , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Leaves/chemistry , Steroids/isolation & purificationABSTRACT
Four new diterpenoids, named aspidoptoids A-D (1-4), together with two known analogues (5-6) were isolated from Aspidopterys obcordata vine. Aspidoptoids A-B (1-2) are the first examples of phenylethylene-bearing 20-nor-diterpenoids of which aspidoptoid B (2) possesses a rare 3,10-oxybridge. Their structures and absolute configuration were determined by extensive spectroscopic analyses (IR, HRESIMS, 1D and 2D NMR) and electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their cytotoxic activities and inhibitory effects on the nitric oxide (NO) production.
