Molecular docking, synthesis, and biological evaluation of naphthoquinone as potential novel scaffold for H5N1 neuraminidase inhibition

Abstract

A series of dimeric naphthoquinones containing natural 2-hydroxy-1-4-naphthoquinone moiety was designed, synthesized, and evaluated against neuraminidase of H5N1 virus. p-hydroxy derivatives showed higher inhibition when compared to p-halogenated compounds. Molecular docking studies conducted with H5N1 neuraminidase clearly demonstrated different binding modes of the most active compound onto the open and closed conformations of loop 150. The results thus provide not only evidences of a novel scaffold evaluated as inhibitor, but also a rational explanation involving molecular modeling and the role of loop 150 in the binding.

Keywords:

• neuraminidase
• H5N1
• molecular docking
• naphthoquinone
• lawsone

Acknowledgments

Garima Sharma and S. Vasanth Kumar thank the management and administration of Karunya University for their encouragement and support.

Disclosure statement

The authors declare no conflict of interest.