Two series of tanshinone ⅡA derivatives were synthesized and evaluated for their antitumor activities as Cdc25 phosphatase inhibitors. Most of them demonstrated potent Cdc25 inhibitory activity and powerful cytotoxic...Two series of tanshinone ⅡA derivatives were synthesized and evaluated for their antitumor activities as Cdc25 phosphatase inhibitors. Most of them demonstrated potent Cdc25 inhibitory activity and powerful cytotoxicity against A549 tumor cell line, producing IC50 values in very low micromolar range. At last, the preliminary SAR was discussed.展开更多
Objective: To screen and evaluate the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25phosphatase. Methods: The affinity chromatography purified glutashione-S-transferase/Cdc25A phosphatase...Objective: To screen and evaluate the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25phosphatase. Methods: The affinity chromatography purified glutashione-S-transferase/Cdc25A phosphatase fusion protein and Cdc2/cyclin B from the extracts of starfish M phase oocytes are used as the cell cycle-specific targets for screening the antimitotic constituents. We tested 9 extracts isolated from the Chinese medicinal herbs and vegetables including the agents currently used in cancer treatment by measuring the inhibition of Cdc25A phosphatase and Cdc2 kinase activity. The antitumor activity of the extracts was also evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry.Results: Cdc25A inhibitory activity and antitumor activity are detected in the extracts isolated from three Chinese medicinal herbs Agrimonapilosa; Herba solani lyrati; Galla chinesis. Conclusion: We found three extracts isolated from Chinese medicinal herbs have potential inhibitory activity of Cdc25 phosphatase using a highly specific mechanism-based screen assay for antimitotic drug discovery.展开更多
Cdc25 phosphatase have been regarded as attractive drug targets for anticancer therapies due to the correlation of their over expression with a wide variety of cancers. They are key regulators of cell cycle progressio...Cdc25 phosphatase have been regarded as attractive drug targets for anticancer therapies due to the correlation of their over expression with a wide variety of cancers. They are key regulators of cell cycle progression and play a central role in the checkpoint response to DNA damage. The role of Cdc25 s in cancer has become increasingly evident in recent years. More than 20 studies of patient samples are from diverse cancers show significant overexpression of Cdc25 with frequent correlation to clinical outcome. Recent screening and design efforts have yielded novel classes of inhibitors that show specificity for the Cdc25 s over other phosphatases and cause cell cycle arrest in vivo. Until now, quinone derivatives are among the most efficient inhibitors of Cdc25 phosphatase activity. Our research objective is to study the inhibition of the phosphathase Cdc25 through the molecular modeling methods.展开更多
基金support by program for New Century Excellent Talents in University (NCET)National Natural Science Foundation of China(No.305722321)Lab of Organic Functional Molecules,the Sino-French Institute of ECNU for supports.
文摘Two series of tanshinone ⅡA derivatives were synthesized and evaluated for their antitumor activities as Cdc25 phosphatase inhibitors. Most of them demonstrated potent Cdc25 inhibitory activity and powerful cytotoxicity against A549 tumor cell line, producing IC50 values in very low micromolar range. At last, the preliminary SAR was discussed.
文摘Objective: To screen and evaluate the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25phosphatase. Methods: The affinity chromatography purified glutashione-S-transferase/Cdc25A phosphatase fusion protein and Cdc2/cyclin B from the extracts of starfish M phase oocytes are used as the cell cycle-specific targets for screening the antimitotic constituents. We tested 9 extracts isolated from the Chinese medicinal herbs and vegetables including the agents currently used in cancer treatment by measuring the inhibition of Cdc25A phosphatase and Cdc2 kinase activity. The antitumor activity of the extracts was also evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry.Results: Cdc25A inhibitory activity and antitumor activity are detected in the extracts isolated from three Chinese medicinal herbs Agrimonapilosa; Herba solani lyrati; Galla chinesis. Conclusion: We found three extracts isolated from Chinese medicinal herbs have potential inhibitory activity of Cdc25 phosphatase using a highly specific mechanism-based screen assay for antimitotic drug discovery.
文摘Cdc25 phosphatase have been regarded as attractive drug targets for anticancer therapies due to the correlation of their over expression with a wide variety of cancers. They are key regulators of cell cycle progression and play a central role in the checkpoint response to DNA damage. The role of Cdc25 s in cancer has become increasingly evident in recent years. More than 20 studies of patient samples are from diverse cancers show significant overexpression of Cdc25 with frequent correlation to clinical outcome. Recent screening and design efforts have yielded novel classes of inhibitors that show specificity for the Cdc25 s over other phosphatases and cause cell cycle arrest in vivo. Until now, quinone derivatives are among the most efficient inhibitors of Cdc25 phosphatase activity. Our research objective is to study the inhibition of the phosphathase Cdc25 through the molecular modeling methods.
