Synthesis of Oxindole-Based Bioorganometallic Kinase Inhibitors Incorporating One or More Ferrocene Groups

A series of oxindole-containing ferrocenes has been synthesized, studied in the solid state by X-ray crystallography, and tested for in vitro kinase inhibition. Many compounds show low or submicromolar activities against DYRK isoforms and VEGFR2, which in certain cases have been rationalized by molecular docking studies

Synthesis of Oxindole-Based Bioorganometallic Kinase Inhibitors Incorporating One or More Ferrocene Groups

A series of oxindole-containing ferrocenes has been synthesized, studied in the solid state by X-ray crystallography, and tested for in vitro kinase inhibition. Many compounds show low or submicromolar activities against DYRK isoforms and VEGFR2, which in certain cases have been rationalized by molecular docking studies

Targeting Epidermal Growth Factor Receptor with Ferrocene-Based Kinase Inhibitors

A series of ferrocene analogues based on a 6,7-dimethoxy-<i>N</i>-phenylquinazolin-4-amine template has been synthesized, and two compounds were characterized in the solid state by X-ray crystallography. The compounds have been tested for in vitro anticancer activity, against epidermal growth receptor (EGFR), and submicromolar IC₅₀ values have been determined

Synthesis and Biological Evaluation of JAHAs: Ferrocene-Based Histone Deacetylase Inhibitors

<i>N</i>¹-Hydroxy-<i>N</i>⁸-ferrocenyloctanediamide, JAHA (<b>7</b>), an organometallic analogue of SAHA containing a ferrocenyl group as a phenyl bioisostere, displays nanomolar inhibition of class I HDACs, excellent selectivity over class IIa HDACs, and anticancer action in intact cells (IC₅₀ = 2.4 μM, MCF7 cell line). Molecular docking studies of <b>7</b> in HDAC8 (a,b) suggested that the ferrocenyl moiety in <b>7</b> can overlap with the aryl cap of SAHA and should display similar HDAC inhibition, which was borne out in an in vitro assay (IC₅₀ values against HDAC8 (μM, SD in parentheses): SAHA, 1.41 (0.15); <b>7</b>, 1.36 (0.16). Thereafter, a small library of related JAHA analogues has been synthesized, and preliminary SAR studies are presented. IC₅₀ values as low as 90 pM toward HDAC6 (class IIb) have been determined, highlighting the excellent potential of JAHAs as bioinorganic probes

Human Pleckstrin Homology domain Interacting Protein (PHIP); A Target Enabling Package

<p>SGC Oxford has expressed, purified and crystallized the second bromodomain of PHIP as part of the probe programme. Fragment screening and X-ray crystallography identified binders, some of which optimised to uM affinity. However, molecules with probe properties were not obtained. Consequently it has been decided to put the information generated into the public domain.</p

Human Pleckstrin Homology domain Interacting Protein (PHIP); A Target Enabling Package

<p>SGC Oxford has expressed, purified and crystallized the second bromodomain of PHIP as part of the probe programme. Fragment screening and X-ray crystallography identified binders, some of which optimised to uM affinity. However, molecules with probe properties were not obtained. Consequently it has been decided to put the information generated into the public domain.</p