Computer-based discovery of SIRT7 inhibitors from Nigella sativa for cancer treatment

Background

SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, is implicated in tumorigenesis, making it a promising therapeutic target for cancer treatment.

Aim

This study aims to identify potent and selective bioactive candidate inhibitors of SIRT7 by virtually screening small-molecule compounds derived from Nigella sativa (N. sativa) and evaluating their drug-likeness and physical stability using computational methods.

Methods

The structure of SIRT7 was retrieved from the RCSB Protein Data Bank (PDB), and N. sativa-derived small molecules were obtained from the PubChem database. Molecular docking was performed using PyRx 0.8 and PyMOL version 2.3.3. Pharmacokinetic parameters and antitumor effects were assessed using SwissADME, pkCSM, and PASS analysis. Furthermore, binding stability was checked through Molecular Dynamics (MD) Simulationusing Schrödinger's Desmond v3.6 program for 100 ns.

Results

From 159 N. sativa-derived compounds, Chrysin, Pinocembrin, Nigellidine, Nigellicine, and Epicatechin showed high binding affinities (−9.3 to −8.7 kcal/mol) and favorable oral bioavailability with low toxicity. Chrysin (CID: 5281607) exhibited the strongest binding score (−9.3 kcal/mol), stable hydrogen bonding, and robust pharmacokinetic properties. PASS analysis highlighted predicted anticancer activities including TP53 activation, apoptosis induction, and antimutagenic effects, particularly for Chrysin, Pinocembrin, and Epicatechin. MD simulation confirmed stable SIRT7–Chrysin interactions, supported by favorable MM/GBSA free energy (−77.11 kcal/mol).

Conclusion

This study highlights N. sativa phytochemicals as potential SIRT7 inhibitors, with Chrysin as the lead candidate and Pinocembrin and Nigellidine as additional promising compounds. The findings offer a computational framework for future validation and development of selective SIRT7-targeted anticancer therapeutics.