Document Type

Article

Publication Date

10-27-2022

Publication Title

Journal of Medicinal Chemistry

Abstract

Sialidases, or neuraminidases, are enzymes that catalyze the hydrolysis of sialic acid (Sia)-containing molecules, mostly removal of the terminal Sia (desialylation). By desialylation, sialidase can modulate the functionality of the target compound and is thus often involved in biological pathways. Inhibition of sialidases with inhibitors is an important approach for under-standing sialidase function and the underlying mechanisms and could serve as a therapeutic approach as well. Transition-state analogues, such as anti-influenza drugs oseltamivir and zanamivir, are major sialidase inhibitors. In addition, difluoro-sialic acids were developed as mechanism-based sialidase inhibitors. Further, fluorinated quinone methide-based suicide substrates were reported. Sialidase product analogue inhibitors were also explored. Finally, natural products have shown competitive inhibiton against viral, bacterial, and human sialidases. This Perspective describes sialidase inhibitors with different mechanisms and their activities and future potential, which include transition-state analogue inhibitors, mechanism-based inhibitors, suicide substrate inhibitors, product analogue inhibitors, and natural product inhibitors.

Comments

The authors acknowledge the research support by research grant from the National Institutes of Health under award no. 1R15GM144881-01, Faculty Research Development Grant from Cleveland State University, and the Research Fund from the Center for Gene Regulation in Health and Disease (GRHD) at Cleveland State University.

DOI

10.1021/acs.jmedchem.2c01258

Volume

65

Issue

20

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