| In vitro: |
| Fitoterapia. 2000 Jun;71(3):317-20. | | Antifungal activity of some tetranortriterpenoids.[Pubmed: 10844171] |
METHODS AND RESULTS:
Natural tetranortriterpenoids such as cedrelone from Toona ciliata, azadiradione from Azadirachta indica, limonin, Limonol and nomilinic acid from Citrus medica, along with some cedrelone derivatives were tested for their antifungal activity against Puccinia arachidis, a groundnut rust pathogen. Results show that cedrelone was the most effective in reducing rust pustule emergence.
CONCLUSIONS:
Replacement of functional groups or modification of the A or the B ring in cedrelone reduced the effectiveness indicating the importance of specific structural features for activity. | | Chemistry. 2016 Sep 5;22(37):13236-50. | | Identification of Limonol Derivatives as Heat Shock Protein 90 (Hsp90) Inhibitors through a Multidisciplinary Approach.[Pubmed: 27492719 ] | The identification of inhibitors of Hsp90 is currently a primary goal in the development of more effective drugs for the treatment of various types of multidrug resistant malignancies.
METHODS AND RESULTS:
In an attempt to identify new small molecules modulating the activity of Hsp90, we screened a small library of tetranortriterpenes. A high-affinity interaction with Hsp90 inducible form was uncovered for eight of these compounds, five of which are described here for the first time. By monitoring the ATPase activity and the citrate synthase thermal induced aggregation, compound 1 (cedrelosin A), 3 (7α-limonylacetate), and 5 (cedrelosin B), containing a Limonol moiety, were found to be the most effective in compromising the Hsp90α chaperone activity. Consistent with these findings, the three compounds caused a depletion of c-Raf and pAkt Hsp90 client proteins in HeLa and MCF/7 cell lines. Induced fit docking protocol and molecular dynamics were used to rationalize the structural basis of the biological activity of the Limonol derivatives.
CONCLUSIONS:
Taken together, these results point to Limonol-derivatives as promising scaffolds for the design of novel Hsp90α inhibitors. |
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