Based on our previous discovery of an anthraquinone scaffold mimicking two faces of Bim α-helix, we derived a quinazolone scaffold through structure simplification and optimization. It was inferred that a rigid bicyclic ring was necessary and efficient to maintain the two-faced binding mode. A novel dual inhibitor 6c [6,7,8-trihydroxy-3-(2-hydroxy-5-methylbenzyl)-2-phenylquinazolin-4(3H)-one] was obtained based on this scaffold. 6c exhibited dual binding activity with K(i) values of 0.123 μM for Mcl-1 and 0.179 μM for Bcl-2.
Keywords: Bcl-2; JQFLKAJQKGNCSW-UHFFFAOYSA-N; Mcl-1; Quinazolone; RNUPWQDKOJAKGW-UHFFFAOYSA-N; SYEGIOUDEHFYQT-UHFFFAOYSA-N; Two-faced; UGGKGLCTXKBKQS-UHFFFAOYSA-N; α-Helix.
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