Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Mechanism of Action of Novel Glibenclamide Derivatives on Potassium and Calcium Channels for Insulin Secretion

Author(s): Marisa Jadna Silva Frederico, Allisson Jhonatan Gomes Castro, Danusa Menegaz, Cahue De Bernardis Murat, Camila Pires Mendes, Alessandra Mascarello, Ricardo Jose Nunes, Fatima Regina Mena Barreto Silva.

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Abstract:

Glibenclamide is widely used and remains a cornerstone and an effective antihyperglycemic drug. After the casual discovery of its hypoglycemic potential, this compound was introduced for diabetes treatment. However, the long-term side effects reveal that glibenclamide should be replaced by new molecules able to maintain the health of β-cells, protecting them from hyperstimulation/hyperexcitability, hyperinsulinemia, functional failure and cell death. The aim of this review was to highlight the main mechanism of action of glibenclamide and the influence of its derivatives, such as acylhydrazones, sulfonamides and sulfonylthioureas on β-cells potassium and calcium channels for insulin secretion as well as the contribution of these new compounds to restore glucose homeostasis. Furthermore, the role of glibenclamide-based novel structures that promise less excitability of β-cell in a long-term treatment with effectiveness and safety for diabetes therapy was discussed.

Keywords: Acyl-hydrazones, glibenclamide derivatives, glucose homeostasis, insulin, pancreatic β-cell, sulfonamides, sulfonylthioureas, sulfonylureas.

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Article Details

VOLUME: 18
ISSUE: 6
Year: 2017
Page: [641 - 650]
Pages: 10
DOI: 10.2174/1389450117666160615084752
Price: $58