- Out of the active site binding pocket for carbonic anhydrase inhibitors
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A structural study of the adduct which 2-benzylsulfinylbenzoic acid forms with human carbonic anhydrase II is reported, showing a binding mode completely different from any other class of carbonic anhydrase inhibitors investigated so far; this carboxylate binds in a pocket situated out of the enzyme active site. This journal is
- D'Ambrosio, Katia,Carradori, Simone,Monti, Simona M.,Buonanno, Martina,Secci, Daniela,Vullo, Daniela,Supuran, Claudiu T.,De Simone, Giuseppina
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- Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold
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A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives.
- Rotondi, Giulia,Guglielmi, Paolo,Carradori, Simone,Secci, Daniela,De Monte, Celeste,De Filippis, Barbara,Maccallini, Cristina,Amoroso, Rosa,Cirilli, Roberto,Akdemir, Atilla,Angeli, Andrea,Supuran, Claudiu T.
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p. 1400 - 1413
(2019/08/26)
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- Enantioselective oxidation of thioethers to sulfoxides by means of a structural template with chiral-at-metal ruthenium complexes
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Treatment of cis-[Ru(bpy)2Cl2]·2H2O or Δ/Λ-[Ru(bpy)2(py)2]2+ (bpy=2,2′-bipyridine, py=pyridine) with the prochiral thioether ligands 2-alkylthiobenzoic acid (HOS-R) produces the corresponding thioether complexes rac-[Ru(bpy)2(OS-R)](PF6) (R=Me (rac-1), iPr (rac-2), 2-benzylthiobenzonate (Bn) (rac-3)) and Δ/Λ-[Ru(bpy)2(OS-R)](PF6) (R=Me (Δ-1/Λ-1), iPr (Δ-2/Λ-2), Bn (Δ-3/Λ-3)) with retention of the configurations at chiral metal centers. In situ oxidation of the thioether complexes by metachloroperoxybenzoic acid provides the corresponding sulfoxide complexes rac-[Ru(bpy)2(OSO-R)](PF6) (OSO-R is 2-alkylsulfinylbenzonate, R=Me (rac-1a), iPr (rac-2a), Bn (rac-3a)), Δ-[Ru(bpy)2{(R)-OSO-R}](PF6) (R=Me (Δ-1a), iPr (Δ-2a), Bn (Δ-3a)), and Λ-[Ru(bpy)2{(S)-OSO-R}](PF6) (R=Me (Λ-1a), iPr (Λ-2a), Bn (Λ-3a)) in yields of 95% with 98% ee values. The absolute configurations at the metal centers and sulfur atoms were determined by means of X-ray crystallography. The results indicate that the configurations of the metal centers are retained and have the function of controlling sulfoxide chirality during the oxidation process. The Δ metal-centered configuration enantioselectively generates an R-configuration sulfoxide, and the Λ configuration enantioselectively forms an S-configuration sulfoxide in the course of the in situ oxidation reaction, thereby resulting in a predetermined chirality of the sulfoxide ligands. The predetermined chirality of sulfoxides (S)-HOSO-R and (R)-HOSO-R were obtained by the treatments of the corresponding sulfoxide complexes Δ-[Ru(bpy)2{(R )-OSO-R}](PF6) and Λ-[Ru(bpy)2{(S)-OSO-R}](PF6) with trifluoroacetic acid in yields of 90% with 83.5-92.9% ee values.
- Li, Zheng-Zheng,Yao, Su-Yang,Ye, Bao-Hui
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p. 141 - 150
(2015/02/05)
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- Intermediates for preparing hipolipemic agents and method of lowering the blood lipid level in mammals with said agents
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Intermediates for preparing benzylthio-, benzylsulfinyl-, and benzylsylfonyl-benzoic acids, and method of lowering the blood lipid level in mammals employing said acids.
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