Evaluation of quinazolin-4-piperidine sulfamides as inhibitors of human NPP1 : relevance in the treatment of pathologic mineralization of valve interstitial cells

Authors: Shayhidin, Elnur Elyar
Advisor: Mathieu, PatrickPibarot, Philippe
Abstract: Calcific aortic valve disease (CAVD) is the most common valvular disorder in the elderly population in the developed counties with the only valid treatment option today remains the aortic valve repair or replacement. The identification of the role of an ectonucleotidase enzyme NPP1 in the process of calcification shed new light into the development of a pharmacological inhibitor that may prevent the calcification of the aortic valve. By far, the compounds that have been developed as inhibitors of NPP1 lack potency and specificity. In the current study, we showed that the quinazolin-4-piperidin sulfamide derivatives to be a potent, specific, and non-competitive inhibitors of NPP1. We also provided evidence that by inhibiting NPP1 enzyme activity these derivatives are able to prevent phosphate-induced mineralization of valve interstitial cells (VICs), the main cellular component of the aortic valve, by preventing both apoptosis and osteoblastic transitions of VICs.
Document Type: Mémoire de maîtrise
Issue Date: 2016
Open Access Date: 24 April 2018
Permalink: http://hdl.handle.net/20.500.11794/26750
Grantor: Université Laval
Collection:Thèses et mémoires

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