New nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold: Design, synthesis, in silico and in vitro studies.

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Alexandru SavaLenuţa Profire

Abstract

In this study we present design and synthesis of nineteen new nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold (NO-IND-TZDs) (6a-s), as a new safer and efficient multi-targets strategy for inflammatory diseases. The chemical structure of all synthesized derivatives (intermediaries and finals) was proved by NMR and mass spectroscopic analysis. In order to study the selectivity of NO-IND-TZDs for COX isoenzymes (COX-1 and COX-2) a molecular docking study was performed using AutoDock 4.2.6 software. Based on docking results, COX-2 inhibitors were designed and 6o appears as the most selective derivative which showed an improved selective index compared with indomethacin (IND) and diclofenac (DCF), used as reference drugs. The biological evaluation of 6a-s, using in vitro assays has included the anti-inflammatory and antioxidant effects as well as the nitric oxide (NO) release. Referring to the anti-inflammatory effects, the most active compound was 6i, which was more active than IND and aspirin (ASP) in term of denaturation effect, on bovine serum albumin (BSA), as indirect assay to predict the anti-inflammatory effect. An appreciable anti-inflammatory effect, in reference with IND and ASP, was a...Continue Reading

References

Apr 1, 1992·Proteins·A L MorrisJ M Thornton
Mar 1, 1968·The Journal of Pharmacy and Pharmacology·Y Mizushima, M Kobayashi
Jun 2, 2001·Alternatives to Laboratory Animals : ATLA·A NovilloA Castaño
Aug 8, 2002·Neuron·Tony Wyss-Coray, Lennart Mucke
Dec 21, 2002·The Journal of Organic Chemistry·Xini ZhangDawei Xu
Aug 20, 2003·The Journal of Biological Chemistry·Scott W RowlinsonLawrence J Marnett
Sep 10, 2003·Drug Discovery Today·Hongshi Yu, Adedayo Adedoyin
Jan 5, 2007·Annual Review of Biophysics and Biomolecular Structure·Michael K Gilson, Huan-Xiang Zhou
Mar 8, 2007·Journal of Medicinal Chemistry·Anna L Blobaum, Lawrence J Marnett
Apr 7, 2007·Alternatives to Laboratory Animals : ATLA·Anatoly S LoukianovAleksander M Korolev
Oct 13, 2007·The Journal of Organic Chemistry·Lai C Chan, Brian G Cox
Feb 1, 2008·Inflammopharmacology·J N SharmaS S Parvathy
Feb 2, 2008·Methods in Enzymology·Martin N Hughes
Jul 25, 2008·Nature·Ruslan Medzhitov
Nov 26, 2008·Arthritis Research & Therapy·Angel Lanas
Sep 3, 2010·The Journal of Biological Chemistry·Kelsey C DugganLawrence J Marnett
Dec 17, 2010·Methods in Molecular Biology·David G Hirst, Tracy Robson
Jul 1, 2009·Molecular Medicine Reports·Lloyd F AlfonsoG J Bhat
Jul 13, 2011·Langmuir : the ACS Journal of Surfaces and Colloids·Maria del Carmen Gimenez-LopezAndrei N Khlobystov
Nov 25, 2011·Expert Review of Clinical Pharmacology·Kathleen M KnightsJohn O Miners
May 16, 2013·Bioorganic & Medicinal Chemistry·Krzysztof SztankeMałgorzata Sztanke
Jun 20, 2013·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Ashok PabbathiAnunay Samanta
Jan 1, 2012·Pharmaceuticals·Luiza Rosaria Sousa Dias, Raquel Rocha Silva Salvador
May 31, 2014·British Journal of Cancer·L AlfonsoG J Bhat
Jun 24, 2014·Current Opinion in Pharmacology·Napapan KangwanKi Baik Hahm
Jul 11, 2014·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Tomoko ShimamuraHiroyuki Ukeda
Aug 31, 2014·Drug Discovery Today·Andreas Koeberle, Oliver Werz
Dec 17, 2014·Journal of the American Chemical Society·Jinping LeiYingkai Zhang
Mar 22, 2015·Drug Discovery Today·Avaneesh K DwivediNagendra Singh
Apr 11, 2015·Journal of Medicinal Chemistry·Douglas E V PiresDavid B Ascher
Feb 13, 2016·Headache·Sylvia Lucas
Mar 30, 2016·Nature Reviews. Drug Discovery·James N Fullerton, Derek W Gilroy
May 15, 2016·Bioorganic & Medicinal Chemistry·Sophie Huber-VillaumeHervé Schohn
May 31, 2016·Trends in Cardiovascular Medicine·Preethi Pirlamarla, Rachel M Bond
Oct 7, 2016·International Journal of Immunopathology and Pharmacology·Chethan Gejjalagere Honnappa, Unnikrishnan Mazhuvancherry Kesavan
Dec 4, 2016·Molecular & Cellular Proteomics : MCP·Michael H TathamRonald T Hay
Dec 13, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sahil KumarT R Bhardwaj
Jan 18, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Adriano MollicaRomano Silvestri

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