AI Article Synopsis
- - A series of bis(benzo[b]furan-2-yl)methanones were created to test their ability to inhibit FLT3 and PDGFR autophosphorylation.
- - The study found that substituting at the C-5 position generally favored PDGFR selectivity, particularly with the 5,5'-dimethoxy variant, while 5,5'-diamino and 6,6'-dihydroxy compounds showed better activity against FLT3.
- - Molecular modeling indicated that these compounds could occupy the same binding site as indole analogues, hinting at a potential weak interaction that could enhance their inhibitory effects.
Article Abstract
A series of bis(benzo[b]furan-2-yl)methanones was synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. Mostly, C-5 substitution leads to PDGFR selectivity, which was strongest in the case of the 5,5'-dimethoxy derivative. The 5,5'-diamino and the 6,6'-dihydroxy compounds are more active at FLT3. At both kinases, the potency of the best inhibitors approaches IC50 values of ca. 0.5 microM. Molecular modeling studies suggest that the bisbenzofuranylmethanones are able to fit into the same binding site as their indolyl analogues which have been suggested to form a bidentate hydrogen bridge with the backbone in the hinge regions. The loss of one H bond by the NH-O exchange might be partially compensated by, for example, the weak interaction of one furanyl oxygen with FLT3 Cys-828.
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| http://dx.doi.org/10.1016/j.bmc.2006.12.011 | DOI Listing |
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