Portuguese researchers, in collaboration with the University of Barcelona, developed new semisynthetic natural products with remarkable antitumor activity

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Portuguese researchers, in collaboration with the University of Barcelona, developed new semisynthetic natural products with remarkable antitumor activity

Monday, 11.09.2017

Authors and Affiliations:

Sandra A.C. Figueiredo a, b, Jorge A.R. Salvador a, b, Roldán Cortés c, Marta Cascante c

a Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Coimbra, 3000-548, Coimbra, Portugal

b Centre for Neuroscience and Cell Biology, Coimbra, Portugal

c Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine, University of Barcelona, Diagonal 643, 08028 Barcelona, Spain.

 

Abstract:

Celastrol is cialisfrance24.com one of the most active antitumour compounds among the natural triterpenoids. A series of new celastrol derivatives have been synthesised and analysed for their biological activity against human cancer cell lines. Several compounds presented a stronger growth inhibition effect than celastrol on the cell lines studied. Among them, compound 24 was the most promising derivative, as it exhibited both a remarkable antiproliferative activity and an improved selectivity in tumour versus non-tumour cells. The anticancer molecular mechanism of compound 24 in the human ovary cancer cell line SKOV-3 was further studied and the results showed that compound 24 induced apoptosis through the activation of the extrinsic death receptor pathway. Interestingly, the results revealed that compound 24 might be able to decrease the levels of dysfunctional p53. The assays also suggested that compound 24 is an Hsp90 inhibitor, and that the Akt/mTOR pathway might be involved in the downstream regulation that leads to its antiproliferative activity. Moreover, a synergistic anticancer effect was evidenced when SKOV-3 cells were simultaneously treated with compound 24 and cisplatin. Taken together, these results suggest that compound 24 may be a promising lead for the development of new cancer therapies.

 

Journal: European Journal of Medicinal Chemistry – Elsevier

 

Link: http://www.sciencedirect.com/science/article/pii/S0223523417304750?via%3Dihub