906635-40-3Relevant academic research and scientific papers
Simplification of the tetracyclic SIRT1-selective inhibitor MC2141: Coumarin- and pyrimidine-based SIRT1/2 inhibitors with different selectivity profile
Rotili, Dante,Carafa, Vincenzo,Tarantino, Domenico,Botta, Giorgia,Nebbioso, Angela,Altucci, Lucia,Mai, Antonello
, p. 3659 - 3668 (2011/08/03)
In this report we describe the synthesis and biological characterization of two series of sirtuins' inhibitors (SIRTi), designed as simplification products of the previously reported SIRT1-selective inhibitor MC2141 (4). In the first series (5a-t) we report a number of 2-substituted-1,2-dihydrobenzo[f]chromen-3- ones with a marked selectivity for the inhibition of SIRT2 over SIRT1. Some of such derivatives showed also high pro-apoptotic (5i and 5l) and/or cytodifferentiating (5d, 5i, and 5o) properties in a human leukemia cell line (U937). The second group of SIRTi (6a-q) is characterized by some analogues of cambinol (3), a well known SIRTi active against the Burkitt lymphoma. Such compounds, differently from the unselective prototype, are endowed with a selective inhibition of SIRT1 over SIRT2, and, in some cases (6j, 6k, and 6q), are more efficient than 3 to induce apoptosis in U937 cells.
PYRIMIDE DERIVATIVES AND THEIR PHARMACEUTICAL USE
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Page/Page column 32-33, (2010/04/27)
The invention provides a compound according to formula (I): wherein: X is O or S; Y is O or S; each Ar and Ar' is independently a mono-, bi- or tricyclic aryl or heteroaryl group optionally substituted with one or more substituents selected from halo, alk
Novel cambinol analogs as sirtuin inhibitors: Synthesis, biological evaluation, and rationalization of activity
Medda, Federico,Russell, Rupert J. M.,Higgins, Maureen,McCarthy, Anna R.,Campbell, Johanna,Slawin, Alexandra M. Z.,Lane, David P.,Lain, Sonia,Westwood, Nicholas J.
supporting information; experimental part, p. 2673 - 2682 (2010/01/16)
The tenovins and cambinol are two classes of sirtuin inhibitor that exhibit antitumor activity in preclinical models. This report describes modifications to the core structure of cambinol, in particular by incorporation of substitutents at the N1-position, which lead to increased potency and modified selectivity. These improvements have been rationalized using molecular modeling techniques. The expected functional selectivity in cells was also observed for both a SIRT1 and a SIRT2 selective analog.
