- Ninhydrins inhibit carbonic anhydrases directly binding to the metal ion
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Ninhydrins show extensive application in organic chemistry and agriculture whereas they have been poorly investigated as bioactive molecules for medicinal chemistry purposes. A series of ninhydrin derivatives was here investigated for the inhibition of human carbonic anhydrases (CAs, EC 4.2.1.1), based on earlier evidence that gem diols are able to coordinate the metal ion from the CA active site. Ninhydrins demonstrated a micromolar inhibitory action against CA I and IX (KIs in the range 0.57–68.2 μM) and up to a nanomolar efficacy against CA II and VII (KIs in the range 0.025–78.2 μM), validated isoforms as targets in several CNS-related diseases. CA IV was instead weakly or poorly inhibited. A computational protocol based on docking, MM-GBSA and metadynamics calculations was used to elucidate the putative binding mode of this type of inhibitors to CA II and CA VII. The findings of this study testify that such pharmacologically underestimated ligands may represent interesting lead compounds for the development of CA inhibitors possessing an innovative mechanism of action, i.e., mono- or bis-coordination to the zinc ion through the diol moiety.
- Bouzina, Abdeslem,Berredjem, Malika,Nocentini, Alessio,Bua, Silvia,Bouaziz, Zouhair,Jose, Joachim,Le Borgne, Marc,Marminon, Christelle,Gratteri, Paola,Supuran, Claudiu T.
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- Microwave-assisted oxidation of indan-1-ones into ninhydrins
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A simple and general microwave-assisted selenium oxidation has been developed for the synthesis of substituted ninhydrins from indan-1-ones in order to access to indeno[1,2-b]indoles substituted on the A ring. This efficient and convenient oxidation, using selenium dioxide under microwave irradiations, afforded mono- and di-substituted ninhydrins in a single step reaction with good yields.
- Marminon, Christelle,Nacereddine, Abdelhamid,Bouaziz, Zouhair,Nebois, Pascal,Jose, Joachim,Le Borgne, Marc
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supporting information
p. 1840 - 1842
(2015/03/30)
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- Synthesis and inhibition study of monoamine oxidase, indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase by 3,8-substituted 5H-indeno[1,2-c]pyridazin-5-one derivatives
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Previous studies on 5H-indeno[1,2-c]pyridazin-5-one derivatives as inhibitors of MAO-B revealed that it was possible to increase the MAO-B inhibitory potency of 5H-indeno[1,2-c]pyridazin-5-ones by substituting the central heterocycle in the 3-position or
- Reniers,Meinguet,Moineaux,Masereel,Vincent,Frederick,Wouters
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supporting information; experimental part
p. 6104 - 6111
(2012/01/13)
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- The Hydration of 1,2,3-Indanetriones and Related Triones
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A series of 5-mono- and 5,6-di-substituted 1,2,3-indanetriones, 1,2,3(2H)-phenalenetrione and 1,3-diphenyl-1,2,3-propanetrione have been shown to form 2,2-dihydroxy-1,3-dione hydrates.The rates for the uncatalysed hydrations has been measured at three temperatures and activation paramaters evaluated.The kinetic role of water and solvent isotope effects have been studied.The Hammett reaction constant, ρ, for the uncatalysed hydration of the substituted 1,2,3-indanetriones in 96.7percent (v/v) dioxane-water at 25 deg C was found to be ca. 1.05.The structure of the transition state for the hydration has been discussed and shown to involve two molecules of water, one acting as a nucleophile and the other as a general acid-base catalyst transferring protons.
- Bowden, Keith,Rumpal, Sanjay
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p. 355 - 374
(2007/10/03)
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- Synthetic routes to ninhydrins. Preparation of ninhydrin, 5-methoxyninhydrin, and 5-(methylthio)ninhydrin
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Two syntheses of 5-methoxyninhydrin (2,2-dihydroxy-5-methoxy-1,3-indanedione) are described. One method employs a novel and efficient two step route, which begins with commercially available 6-methoxy-1-indanone. The application of this strategy for the preparation of a new ninhydrin derivative, 5-(methylthio)ninhydrin, and ninhydrin is also presented.
- Heffner,Joullie
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p. 2231 - 2256
(2007/10/02)
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