Identification and Evaluation of New Potential Inhibitors of Human Neuraminidase 1 Extracted from Olyra latifolia L.: A Preliminary Study

Abstract

Sialidases, also called neuraminidases, are involved in several human pathologies such as neurodegenerative disorders, cancers, as well as infectious and cardiovascular diseases. Several studies have shown that neuraminidases, such as neuraminidase 1 (NEU-1), may be promising pharmacological targets. Therefore, the discovery of new selective inhibitors of NEU-1 are necessary to better understand the biological functions of this sialidase. In the present study, we describe the isolation and characterization of nine known compounds from Olyra latifolia L. leaves. This plant, known to have several therapeutic properties, belongs to the family of Poaceae and is found in the neotropics and in tropical Africa and Madagascar. Among the purified compounds, feddeiketone B, 2,3-dihydroxy-1-(4-hydroxy-3,5-diméthoxyphényl)-l-propanone, and syringylglycerol were shown to present structural analogy with DANA, and their effects on membrane NEU-1 sialidase activity were evaluated. Our results show that they possess inhibitory effects against NEU-1-mediated sialidase activity at the plasma membrane. In conclusion, we identified new natural bioactive molecules extracted from Olyra latifolia as inhibitors of human NEU-1 of strong interest to elucidate the biological functions of this sialidase and to target this protein involved in several pathophysiological contexts.

Human Neuraminidases: Structures and Stereoselective Inhibitors

“…Recently, Albrecht et al . discovered purified compounds derived from Olyra latifolia L. leaves with scaffolds such as 20 , feddeiketone B, 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)- l -propanone, and syringylglycerol, which exert inhibitory effects on NEU1 sialidase activity in the plasma membrane.…”

“…Recently, Albrecht et al 138 discovered purified compounds derived from Olyra latifolia L. leaves with scaffolds such as 20, feddeiketone B, 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-L-propanone, and syringylglycerol, which exert inhibitory effects on NEU1 sialidase activity in the plasma membrane. Further investigation of these compounds may be valuable for elucidating the biological functions of this sialidase and exploring natural bioactive hNEU inhibitors.…”

Sialidase Inhibitors with Different Mechanisms

“…Natural compounds have been explored for human sialidase inhibition in recent studies. Albrecht et al described the identification and evaluation of human Neu1 inhibitor extracted from Olyra latifolia L . Specifically, Feddeiketone B (Figure b), 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)- l -propanone (Figure c), and syringylglycerol (Figure d) show inhibition effects on the cell membrane Neu1 sialidase activity.…”

The Elastin Receptor Complex: An Emerging Therapeutic Target Against Age-Related Vascular Diseases

“…In vivo application of these new promising selective NEU1 inhibitors is currently under investigation. Finally, recent works have been done to identify neuraminidase inhibitors from natural bioactive molecules extracted from plants (90)(91)(92). These natural bioactive compounds could be used as a starting point for the development of new natural putative NEU1 inhibitors and the design of more potent synthetic compounds.…”

“…These natural bioactive compounds could be used as a starting point for the development of new natural putative NEU1 inhibitors and the design of more potent synthetic compounds. In this context, we recently reported the purification of three natural compounds from the leaves of the Olyra latifolia plant that present structural analogy with DANA and possess inhibitory effects against human NEU1 (90).…”