Eight new triterpenoids were isolated from Ainsliaea latifolia.The structures of these compounds were elucidated by interpretation of spectroscopic data,including HRESIMS and NMR data.Compounds 4–6 are identifed as rare trinorcucurbitane or tetranorcucurbitane triterpenoids.The absolute confgurations of compounds 1 and 2 were confrmed by Snatzke’s method.All compounds were evaluated for their inhibition against cyclooxyenase-2(COX-2),in which compound 4 showed signifcant inhibitory efect against COX-2 with IC_(50) value of 3.98±0.32μM,comparable to that of positive control NS-398(IC504.14±0.28μM).
The biflavonoid isochamaejasmin is mainly distributed in the root of Stellera chamaejasme L.(Thymelaeaceae) that is used in traditional Chinese medicine(TCM) to treat tumors, tuberculosis, and psoriasis. Herein, isochamaejasmin was found to show similar bioactivity against Bcl-2 family proteins to the reference Bcl-2 ligand(–)-gossypol through 3D similarity search. It selectively bound to Bcl-xL and Mcl-1 with Ki values being 1.93 ± 0.13 μmol·L-1 and 9.98 ± 0.21 μmol·L-1, respectively. In addition, isochamaejasmin showed slight growth inhibitory activity against HL-60 with IC50 value being 50.40 ± 1.21 μmol·L-1 and moderate growth inhibitory activity against K562 cells with IC50 value being 24.51 ± 1.62 μmol·L-1. Furthermore, isochamaejasmin induced apoptosis of K562 cells by increasing the intracellular expression levels of proteins of the cleavage of caspase-9, caspase-3, and PARP which involved in the Bcl-2-induced apoptosis pathway. These results indicated that isochamaejasmin induces apoptosis in leukemia cells by inhibiting the activity of Bcl-2 family proteins, providing evidence for further studying the underlying anti-cancer mechanism of S. chamaejasme L..
UbcH5c belongs to the ubiquitin-conjugating enzyme family and plays an important role in catalyzing ubiquitination during TNF-α–triggered NF-κB activation. Therefore, UbcH5c is a potent therapeutic target for the treatment of inflammatory and autoimmune diseases induced by aberrant activation of NF-κB. In this study, we established a stable expression system for recombinant UbcH5c and solved the crystal structure of UbcH5c belonging to space group P22_12_1 with one molecule in the asymmetric unit. This study provides the basis for further study of UbcH5c including the design of UbcH5c inhibitors.
Four new 3,4-secocycloartane triterpenoids,pseudolactones A-D(1-4),were isolated from the ethanol extract of the cones of Pseudol arixamabilis.Their structures were established by extensive 1D-and 2D-NMR experiments.The cones of P.arixamabilis are enriched in the ring-expanded or cleaved cycloartane triterpenoids.This work provides new insight into cycloartane triterpenoids from the cones of P.arixamabilis.
We designed and synthesized a series of 2-thioxo-4-thiazolidinone derivatives and evaluated them on peroxisome proliferator activated receptor γ（PPARγ） binding activities.Through the biological assays,compounds 18 and 38 were highlighted with K_i values of 12.15 nmol/Land 14.46 nmol/L,respectively.Then structure-activity relationship（SAR） was analyzed to screen privileged structural modifications.Moreover,molecular fitting of these compounds onto the approved drug Rosightazone in the PPARγligand binding domain was performed to elucidate the SAR and explore potential receptor-ligand interactions.These results demonstrate that the 2-thioxo-4-thiazolidinones can be considered as new promising molecular probes with excellent binding activities to PPARγ.
Li ZhouYe ZhongMeng-Zhu XueDong KuangXian-Wen CaoZhen-Jiang ZhaoHong-Lin LiYu-Fang XuRui Wang
The connectivity map（CMAP） database is established initially to connect biology, chemistry, and clinical conditions, which helps to discover the connection of disease-gene-drug. The CMAP approach has been applied in the field of drug discovery and development, which is widely recognized. In recently years, CMAP analysis has been applied in the research on Chinese materia medica（CMM）. The study of CMM is facing a wide range of challenges, such as complicated ingredients, multiple targets, multiple pathways of action and complex functioning mechanism. The idea of employing CMAP in the CMM research has brought a new perspective for researchers and provides a systematic method for elucidating the mechanism of CMM.The connectivity map （CMAP） database is established initially to connect biology, chemistry, and clinical conditions, which helps to discover the connection of disease-gene-drug. The CMAP approach has been applied in the field of drug discovery and development, which is widely recognized. In recently years, CMAP analysis has been applied in the research on Chinese materia medica （CMM）. The study of CMM is facing a wide range of challenges, such as complicated ingredients, multiple targets, multiple pathways of action and complex functioning mechanism. The idea of employing CMAP in the CMM research has brought a new perspective for researchers and provides a systematic method for elucidating the mechanism of CMM.
