Marine-Based Candidates as Potential RSK1 Inhibitors: A Computational Study

Area of Science:

• Marine Natural Products Chemistry
• Molecular Biology
• Computational Chemistry

Background:

• Manzamines are a class of compounds isolated from the marine sponge *Acanthostrongylophora ingens*.
• Previous research suggested manzamine A may inhibit RSK1 kinase, a potential therapeutic target.

Purpose of the Study:

• To investigate the inhibitory potential of seven identified manzamine compounds against the RSK1 kinase N-terminal domain.
• To correlate in silico docking results with experimental biological activity data.

Main Methods:

• Molecular docking simulations using Autodock Vina software.
• In vitro biological assays to determine inhibitory concentrations (IC50).

Main Results:

• Manzamine A N-oxide (5) exhibited the highest docking score and potent inhibitory activity (IC50 = 3.1 μM).
• Docking scores successfully predicted the biological activity for four compounds, showing concordance between in silico and in vitro data.
• The β-carboline ring and lipophilic side chains were identified as crucial for receptor binding within the RSK1 active site.

Conclusions:

• Manzamine derivatives show promise as RSK1 kinase inhibitors.
• Molecular docking is a valuable tool for predicting the activity of marine natural products.
• Understanding structure-activity relationships can guide the development of novel therapeutic agents.