[5-(Benzyloxy)-1H-indol-1-yl]acetic acid, an aldose reductase inhibitor and PPAR gamma ligand

Prnova, Marta Soltesova
Majekova, Magdalena
Milackova, Ivana
Diez-Dacal, Beatriz
Perez-Sala, Dolores
Ceyhan, Muserref Seyma
Banerjee, Sreeparna
Stefek, Milan
Based on overlapping structural requirements for both efficient aldose reductase inhibitors and PPAR ligands, [5-(benzyloxy)-1H-indol-1-yl] acetic acid (compound 1) was assessed for inhibition of aldose reductase and ability to interfere with PPAR gamma. Aldose reductase inhibition by 1 was characterized by IC50 in submicromolar and low micromolar range, for rat and human enzyme, respectively. Selectivity in relation to the closely related rat kidney aldehyde reductase was characterized by approx. factor 50. At organ level in isolated rat lenses, compound 1 significantly inhibited accumulation of sorbitol in a concentration-dependent manner. To identify crucial interactions within the enzyme binding site, molecular docking simulations were performed. Based on luciferase reporter assays, compound 1 was found to act as a ligand for PPAR gamma, yet with rather low activity. On balance, compound 1 is suggested as a promising lead-like scaffold for agents with the potential to interfere with multiple targets in diabetes.


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Goksu, A; Iltan, EO; Solmaz, L (2001-04-20)
We study the decay width and CP asymmetry of the inclusive process b --> sgg (g denotes gluon) in the three and two Higgs doublet models with complex Yukawa couplings. We analyze the dependencies of the differential decay width and CP asymmetry to the s-quark energy E-s and CP violating parameter theta. We observe that there exist a considerable enhancement in the decay width and CP asymmetry is at the order of 10(-2). Further, it is possible to predict the sign of C-7(eff) using the CP asymmetry.
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Aslan Taşkaya, Sultan; Balcı, Metin; Department of Chemistry (2015)
New methodologies were developed for the synthesis of pyrrolo- and indolo-oxazin1-one derivatives. In the first section of this thesis, various N-propargyl pyrrole and indole esters were efficiently converted into corresponding carboxylic acids which then underwent intramolecular cyclization reaction with AuCl3 to give 6-exo-dig cyclization products. In the second part of the study, 6-exo-dig pyrrolo- and indolo- oxazinone derivatives were treated with TFA in order to achieve double bond isomerization. Some...
The Chemistry of Ethyl 3-(2-Ethoxy-2-oxoethyl)-1H-indole-2-carboxylate: Synthesis of Pyrimido[4,5-b]indoles and Diethyl 4-Hydroxyquinoline-2,3-dicarboxylate via Intramolecular Cyclizations
KAPTI, Tolga; Dengiz, Çağatay; BALCI, METİN (2017-04-01)
We report the synthesis of a new series of 2-oxo-1,2,4,9-tetrahydro- 3H-pyrimido[4,5-b] indole derivatives and diethyl 4-hydroxyquinoline- 2,3-dicarboxylate starting from ethyl 3-(2-ethoxy-2-oxoethyl)- 1H-indole-2-carboxylate. Intramolecular cyclization formed the target ring systems. The key substrates featuring both acyl azide and isocyanate functionalities were prepared from bis(acyl azide) intermediate. The acyl azide functionalities directly connected to methylene groups were regiospecifically converte...
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Türker, Burhan Lemi (Informa UK Limited, 2000-01-01)
Di- and tri- [2(2)]-para-cyclophane fused metal-free tetraazaporpyrins were subjected to AM1 type semiempirical molecular orbital treatment. The calculations predict that they should be stable but endothermic structures. Some quantum chemical and physicochemical properties of them have been presented as well.
Alıyev, Tahmasıb; ILTAN, E; PAK, NK (1995-05-25)
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Citation Formats
M. S. Prnova et al., “[5-(Benzyloxy)-1H-indol-1-yl]acetic acid, an aldose reductase inhibitor and PPAR gamma ligand,” ACTA BIOCHIMICA POLONICA, pp. 523–528, 2015, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/42379.