Abstract
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 8ac, 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 IC50 = 18.79 +/- 0.68 nM relative to Alvespimycin as a reference drug. Finally, molecular modeling of the most active compounds in