In this work the synthesis, structure activity relationship (SAR) and biological evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2 and 3.2 mu M in cell-based and cell-free assays, respectively. Optimization of binding and functional potencies resulted in the identification of compound 13d, which showed an enhanced activity compared to the parent bioactive compound caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were identified as lead compounds in inhibiting 5-LO products formation in neutrophils. Their interference with other targets on the arachidonic acid pathway was also assessed. Cytotoxicity tests were performed to exclude a relationship between cytotoxicity and the increased activity observed after structure optimization. (C) 2015 Published by Elsevier Masson SAS.

Erratum: Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors (European Journal of Medicinal Chemistry (2015) 101 (573-583)) / De Lucia, D.; Lucio, O. M.; Musio, B.; Bender, A.; Listing, M.; Dennhardt, S.; Koeberle, A.; Garscha, U.; Rizzo, R.; Manfredini, S.; Werz, O.; Ley, S. V.. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 103:(2015), pp. 8086.223-8086.225. [10.1016/j.ejmech.2015.07.011]

Erratum: Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors (European Journal of Medicinal Chemistry (2015) 101 (573-583))

De Lucia D.;Musio B.;Rizzo R.;
2015-01-01

Abstract

In this work the synthesis, structure activity relationship (SAR) and biological evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2 and 3.2 mu M in cell-based and cell-free assays, respectively. Optimization of binding and functional potencies resulted in the identification of compound 13d, which showed an enhanced activity compared to the parent bioactive compound caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were identified as lead compounds in inhibiting 5-LO products formation in neutrophils. Their interference with other targets on the arachidonic acid pathway was also assessed. Cytotoxicity tests were performed to exclude a relationship between cytotoxicity and the increased activity observed after structure optimization. (C) 2015 Published by Elsevier Masson SAS.
2015
Erratum: Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors (European Journal of Medicinal Chemistry (2015) 101 (573-583)) / De Lucia, D.; Lucio, O. M.; Musio, B.; Bender, A.; Listing, M.; Dennhardt, S.; Koeberle, A.; Garscha, U.; Rizzo, R.; Manfredini, S.; Werz, O.; Ley, S. V.. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 103:(2015), pp. 8086.223-8086.225. [10.1016/j.ejmech.2015.07.011]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11589/223787
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