Discovery of pyroptosis-inducing natural products in neuroblastomas: computational studies with experimental validation.

ABSTRACT:

Background

Neuroblastomas evade apoptosis due to oncogene mutations and antiapoptotic proteins, necessitating novel therapeutics that work in concert with other forms of cell death. Pyroptosis has potential as a strategic cell death mechanism in neuroblastoma. This study aimed to identify compounds that modulate pyroptosis, specifically those that target gasdermin D (GSDMD) oligomerization.

Methods

The study employed computational analysis and in vitro screening. The COCONUT database provides the natural compound dataset. Drug-likeness analysis and pharmacophore fitting were applied to screen potential GSDMD oligomerization modulators. Hit compounds underwent molecular docking with MOE and molecular dynamic (MD) simulations with NAMD 2.14 to analyse structural changes. The c

SUBMITTER: Lestari B 

PROVIDER: S-EPMC12276684 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature