Quoc K. Wu

Publications (2)9.6 Total impact

• Article: Metallocene-based inhibitors of cancer-associated carbonic anhydrase enzymes IX and XII.

  Adam J Salmon, Michael L Williams, Quoc K Wu, Julia Morizzi, Daniel Gregg, Susan A Charman, Daniela Vullo, Claudiu T Supuran, Sally-Ann Poulsen
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  ABSTRACT: In this study, 20 metallocene-based compounds comprising extensive structural diversity were synthesized and evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. These compounds proved moderate to good CA inhibitors in vitro, with several compounds displaying selectivity for cancer-associated isozymes CA IX and CA XII compared to off-target CA I and CA II. Compound 6 was the most potent ferrocene-based inhibitor with K(i)s of 5.9 and 6.8 nM at CA IX and XII, respectively. A selection of key drug-like parameters comprising Log P, Log D, solubility, and in vitro metabolic stability and permeability were measured for two of the ferrocene-based compounds, regioisomers 1 and 5. Compounds 1 and 5 were found to have characteristics consistent with lipophilic compounds, however, our findings show that the lipophilicity of the ferrocene moiety is not well modeled by replacement with either a naphthyl or a phenyl moiety in software prediction tools.
  Journal of Medicinal Chemistry 04/2012; 55(11):5506-17. · 4.80 Impact Factor
• Article: S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases.

  Marie Lopez, Blessy Paul, Andreas Hofmann, Julia Morizzi, Quoc K Wu, Susan A Charman, Alessio Innocenti, Daniela Vullo, Claudiu T Supuran, Sally-Ann Poulsen
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  ABSTRACT: In this paper, we present a new class of carbonic anhydrase (CA) inhibitor that was designed to selectively target the extracellular domains of the cancer-relevant CA isozymes. The aromatic moiety of the classical zinc binding sulfonamide CA inhibitors is absent from these compounds and instead they incorporate a hydrophilic mono- or disaccharide fragment directly attached to the sulfonamide group to give S-glycosyl primary sulfonamides (1-10). The inhibition properties of these compounds at the physiologically abundant human CA isozymes I and II and cancer-associated IX and XII were determined, and all compounds had moderate potency with K(i)s in the micromolar range. We present the crystal structures of anomeric sulfonamides 4, 7, and 10 and the sugar sulfamate drug topiramate in complex with human recombinant CA II. From these structures, we have obtained valuable insights into ligand-protein interactions of these novel carbohydrate-based sulfonamides with CA.
  Journal of Medicinal Chemistry 10/2009; 52(20):6421-32. · 4.80 Impact Factor