Effective natural inhibitors targeting poly ADP-ribose polymerase by computational study

Area of Science:

• Computational chemistry
• Drug discovery
• Pharmacology

Background:

• Poly (ADP-ribose) polymerase (PARP) is a key target for various therapeutic interventions.
• Identifying novel inhibitors with high efficacy and safety is crucial for drug development.

Purpose of the Study:

• To screen for ideal lead compounds and drug candidates that inhibit PARP using virtual screening.
• To identify potential PARP inhibitors with favorable safety profiles from the ZINC database.

Main Methods:

• Structure-based virtual screening using LibDock.
• Absorption, Distribution, Metabolism, and Excretion (ADME) and toxicity predictions.
• Molecular docking and molecular dynamics simulations to assess binding affinity and complex stability.

Main Results:

• Two natural compounds, ZINC000003938684 and ZINC000014811844, identified as potent PARP binders with high affinity.
• Predicted favorable safety profiles, including low rodent carcinogenicity, Ames mutagenicity, and developmental toxicity.
• Molecular dynamics simulations confirmed stable interactions between the compounds and PARP.

Conclusions:

• ZINC000003938684 and ZINC000014811844 are promising candidates for PARP inhibitors.
• These compounds exhibit desirable safety characteristics, positioning them as viable drug candidates.
• The findings offer valuable insights for the design and enhancement of CMET target drugs.