Research paper1-Aroylindoline-hydroxamic acids as anticancer agents, inhibitors of HSP90 and HDAC

Add time:08/26/2019    Source:sciencedirect.com

A series of 1-aroylindoline-hydroxamic acids have been synthesized in the present study. The results of the biological evaluation led to the identification of compound 12 as dual HDAC6/HSP90 inhibitor. Compound 12 displayed striking inhibitory effects towards the HDAC6 isoform and HSP 90 protein with IC50 values of 1.15 nM (HDAC6) and 46.3 nM (HSP90). Compound 12 also exhibited 113, 139 and 246 fold higher selectivity for HDAC6 over HDAC 1, HDAC 3 and HDAC 8 isoforms and was endowed with significant cytotoxic effects with GI50 values ranging 1.04–1.61 μM against lung A549, colorectal HCT116, leukemia HL60, and EGFR T790M mutant lung H1975 cell lines. Another interesting finding of the study was substantial cytotoxic effects of compounds particularly against lung H1975 (NSCLC) cell lines with IC50 = 0.26 μM which may be mediated through HSP90 inhibition. Compound 8 as such was devoid of HDAC inhibitory activity.

We also recommend Trading Suppliers and Manufacturers of 3-AMINOINDOLIN-2-ONE (cas 117069-75-7). Pls Click Website Link as below: cas 117069-75-7 suppliers

Prev:Original articleDirect construction of 3′,4′-dihydrospiro[pyrrol-3,2′-oxindoles] through a cascade Michael/cyclization reaction of 3-AMINOINDOLIN-2-ONE (cas 117069-75-7)s with enones/enals
Next:Original articleBioisosteric replacement of an acylureido moiety attached to an indolin-2-one scaffold with a malonamido or a 2/4-pyridinoylamido moiety produces a selectively potent Aurora-B inhibitor)