| Autor: |
Alosaimy, Amal M., Abouzied, Amr S., M. R. Alsaedi, Amani, Alafnan, Ahmed, Alamri, Abdulwahab, Alamri, Mubarak A., Khaled Bin Break, Mohammed, Sabour, Rehab, Farghaly, Thoraya A. |
| Zdroj: |
Arabian Journal of Chemistry; Apr2023, Vol. 16 Issue 4, pN.PAG-N.PAG, 1p |
| Abstrakt: |
[Display omitted] • New indene derivatives targeting Hsp90 were synthesized, and biologically evaluated. • Five new indene derivatives displayed significant antitumor effect especially on MCF-7 cell line compared to doxorubicin. • The most active compound 8a showed reduced cytotoxic effect against WI‐38 normal cells, suggesting its high safety profile. • The Hsp90 enzyme assay of 8a displayed IC 50 = 18.79 ± 0.68 nM relative to Alvespimycin as a reference drug. • The molecular modeling of the most active compounds in the Hsp90 binding site was done presenting agreement with the in vitro anti-Hsp90 activity. Inhibition of Heat-shock protein 90 (Hsp90) is considered an attractive route in fighting against cancer proliferation. Herein, new indene derivatives targeting Hsp90 were synthesized, and biologically evaluated. The new series of indeno-pyrimidine and indeno-pyridine were synthesized from the reaction of indene-enaminone with various heterocyclic amines and active methylene derivatives. Two breast cancer cell lines were used to examine the new compounds in vitro for their anticancer activity, namely, MCF-7 and MDA-MB231 cancer cells. The new indene derivatives 8a-c , 17a , and 25 displayed significant antitumor effect especially on MCF-7 cell line compared to doxorubicin. Derivative 8a was further subjected to Hsp90 enzyme assay aiming to ensure the inhibitory potential of such compound on Hsp90, it displayed IC 50 = 18.79 ± 0.68 nM relative to Alvespimycin as a reference drug. Finally, molecular modeling of the most active compounds in the Hsp90 binding site was done presenting agreement with the in vitro anti-Hsp90 activity. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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