Virtual Screening of 1,4-Naphthoquinone Derivatives for Inhibition of a Key Cancer Signaling Protein, AKT1 Kinase

Abstract

Background/aim: AKT, also known as protein kinase B (PKB), is an established therapeutic target in cancer and its inhibitors are increasingly designed. The anti-cancer potential of a compound class naphthoquinones has been constantly realized. The current work aimed to explore AKT1 inhibitors from 1,4-naphthoquionone derivatives.

Materials and methods: A library of 1,4-naphthoquionone derivatives was formed using similarity search and visual analysis. The library was used for virtual screening using molecular docking. For the screened compounds, the detailed binding pose analysis, binding energy and dissociation constant calculations were performed.

Results: The top 10 screened compounds were proposed as potential AKT1 inhibitors with anti-cancer activity. The compounds were checked for any reported activity, and our 2nd rank compound was reported to have anti-cancer activity.

Conclusion: Our study proposes 10 compounds as potential AKT1 inhibitors and anticancer agents and also provides insights into their binding. This study also proposes AKT1 as a potential target of the reported anticancer compound, CID: 341807.

Keywords: AKT; Naphthoquinone; PKB; anti-cancer; inhibitor; protein kinase; virtual screening.