Exploring isoxazoles and pyrrolidinones decorated with the 4,6-dimethoxy-1,3,5-triazine unit as human farnesyltransferase inhibitors.

Autor: Lucescu L; Faculty of Chemistry, Al. I. Cuza' University of Iasi, Iasi, Romania., Ghinet A; Faculty of Chemistry, Al. I. Cuza' University of Iasi, Iasi, Romania.; Inserm U995, LIRIC, Faculté de médecine-Pôle recherche, Université de Lille, CHRU de Lille, Lille, France.; Laboratoire de Chimie Durable et Santé, Hautes Etudes d'Ingénieur (HEI), Yncréa Hauts-de-France, UC Lille, Lille, France., Shova S; Petru Poni' Institute of Macromolecular Chemistry, Iasi, Romania., Magnez R; Univ. Lille, UMR-S 1172 - JPARC - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille, France., Thuru X; Univ. Lille, UMR-S 1172 - JPARC - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille, France., Farce A; Inserm U995, LIRIC, Faculté de médecine-Pôle recherche, Université de Lille, CHRU de Lille, Lille, France.; Faculté des Sciences Pharmaceutiques et Biologiques de Lille, Lille, France., Rigo B; Inserm U995, LIRIC, Faculté de médecine-Pôle recherche, Université de Lille, CHRU de Lille, Lille, France.; Laboratoire de Chimie Durable et Santé, Hautes Etudes d'Ingénieur (HEI), Yncréa Hauts-de-France, UC Lille, Lille, France., Belei D; Faculty of Chemistry, Al. I. Cuza' University of Iasi, Iasi, Romania., Dubois J; Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Gif-sur-Yvette, France., Bîcu E; Faculty of Chemistry, Al. I. Cuza' University of Iasi, Iasi, Romania.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2019 May; Vol. 352 (5), pp. e1800227. Date of Electronic Publication: 2019 Apr 04.
DOI: 10.1002/ardp.201800227
Abstrakt: Unprecedented triazinyl-isoxazoles were afforded via an effective cycloaddition reaction between nitrile oxides and the scarcely described 2-ethynyl-4,6-dimethoxy-1,3,5-triazine as dipolarophile. The biological evaluation of the newly synthesized compounds showed that the inhibition of human farnesyltransferase by zinc complexation could be improved with triazine-isoxazole moieties. The replacement of the isoxazole unit by a pyrrolidin-2-one was detrimental to the inhibitory activity while the pyrrolidin-2-thione derivatives conserved the biological potential. The potential of selected compounds to disrupt protein farnesylation in Chinese hamster ovary (CHO) cells transfected with pEGFP-CAAX was also evaluated.
(© 2019 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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