Discovery and activity verification of reniformin A as an anti-tumor leading compound / 中国中药杂志

Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD_(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.

Novel analgesic targets and corresponding analgesic leading compounds / 中国药理学与毒理学杂志

Opioid medications have been used for pain management, but there are negative side effects, including a potential delay in recovery and increased risk of permanent disability. In this paper, analgesic targets including N-methyl-D-aspartate receptors, cannabinoid receptors, prostaglandin E2 receptor 4 receptors, matrix metalloproteinase receptors, and some new targets for blocking pain signaling pathways associated with these receptors are reviewed. In addition, some novel agonists, antagonists, and leading compounds with agonistic (antagonistic) activities interacting with the target are also described. These novel compounds usually have better analgesic activity and lower side effects than traditional opioids. They are expected to be developed into new analgesics and benefit clin?ical patients who need pain treatment.

Historical story on natural medicinal chemistry: Drugs from ocean / 中草药

Unlike terrestrial organisms, marine organisms have to adapt to extreme marine environmental conditions, and to acclimatize to these conditions, marine organisms possess unique characteristics that differentiate from terrestrial organisms in many aspects, such as metabolism. And this led to marine organisms often produce unique secondary metabolites that have not been observed in terrestrial organisms. Diversity of marine natural products has played a fundamental role in biomedical research and drug development during the last decades, either directly as drugs or as leading compounds that were further optimized by medicinal chemists. From these efforts, 10 approved drugs and dozen current clinical trial agents have been discovered, either as natural products or molecules inspired from the natural product structure. This paper summarized the new drugs developed from marine organisms. This is one of the series papers about "historical story on natural medicinal chemistry".

Design and discovery of novel small-molecule inhibitor of CDK9 / 中国药理学通报

Aim To look for novel small-molecule inhibitors of CDK9 through structure-based virtual screening and biological activity determination.Methods Homology modeling of CDK9 was based on the 3-D structure of other cyclin-dependent kinase family members,and then virtual screening by DOCK(molecular docking)of database of small molecule was carried on.MTT method was used in inhibition of tumor cell growth in vitro,while Western blot was used for further study of molecular mechanisms.Results From the top 1000 compounds with the best DOCK energy score,27 compounds were selected for biological assay based on the diversity of chemical structure and functional group.12 of 27 selected compounds showed significantly inhibition activity on tumor cell proliferation,and only one compound in 12 with half-maximum inhibition concentration(IC50)values less than 20 ?mol?L-1 named C-21 was selected for further molecular mechanism study.The western blotting data showed C-21 compound could effectively inhibit CDK9 from phosphorylating large subunit C-terminal of RNA polymerase Ⅱ in a dose-dependent manner.Conclusions Through homology modeling,virtual screening by computer,determination of biological activity and experimental studies of molecular mechanism,a new promising lead compound targeted for CDK9 was found and confirmed.

Strategy for Screening Leading Compounds From Botanicals / 中国药房

OBJECTIVE:To discuss the strategy for screening new leading compounds and discover the novel drug candidates,which have the independent intelligent property right,from botanicals METHODS:Screening the new leading componds from the single plant which plays the main therapeutic role in classical prescriptions or proved recipes were reviewed RESULTS:The results showed that the frequency of use of certain kinds of plant was higher than that of the others in treatment of certain disease,it is hypothesized that the plant may contain the active ingredient for the therapy of certain kinds of disease CONCLUSION:Screening new leading compound from Chinese materia medica is a shortcut with less risk,which may promote the development of new drugs in China