MUMBAI, India, Jan. 2 -- Intellectual Property India has published a patent application (202541123928 A) filed by Vignan's Foundation For Science, Technology And Research, Vadlamudi, Andhra Pradesh, on Dec. 9, 2025, for 'novel antibacterial dhfr inhibitor identified through pharmacophore-based virtual screening and molecular dynamics simulation.'
Inventor(s) include Dr. Mithun Rudrapal.
The application for the patent was published on Jan. 2, under issue no. 01/2026.
According to the abstract released by the Intellectual Property India: "Methicillin-resistant Staphylococcus aureus (MRSA) remains a critical global health threat, necessitating the development of novel antimicrobial agents. Dihydrofolate reductase (DHFR) represents a validated therapeutic target for antibacterial drug discovery. Objective: This study aimed to identify novel DHFR inhibitors with enhanced efficacy against MRSA through an integrated computational drug design approach. Structure-based pharmacophore modeling was performed using the crystal structure of Staphylococcus aureus DHFR (PDB: 3FYV) complexed with AR-102. Virtual screening of ZINC, MolPort, ChemSpace, and ChEMBL databases identified 94 potential inhibitors. Comprehensive ADMET profiling narrowed the selection to 10 optimal candidates through K-means clustering and multi-parameter optimization. The top five compounds underwent 50 ns molecular dynamics simulations using GROMACS. Results: PubChem-44362961 (5-[(E)-1-(3,4,5-trimethoxyphenyl)prop-1-enyl]pyrimidine-2,4-diamine) emerged as the most promising candidate, exhibiting excellent drug-likeness (QED: 0.8699), favorable ADMET score (0.775), and zero toxicity profile. Molecular docking revealed critical hydrogen bonds with ALA7 and multiple hydrophobic interactions. MD simulations confirmed superior stability with the lowest mean RMSD (0.116 nm 0.018 nm) and optimal protein-ligand complex stability. Ligand 1 maintained key interactions observed in the reference compound while demonstrating enhanced conformational stability. This integrated computational pipeline successfully identified PubChem-44362961 as a potential lead compound for MRSA treatment. The compound retains the successful inhibition mechanism of AR-102 while offering optimized pharmacokinetic properties. These findings provide a rational foundation for developing next-generation DHFR inhibitors against antimicrobial-resistant pathogens. Future experimental validation and structure-activity relationship studies are warranted to advance this compound toward clinical development."
Disclaimer: Curated by HT Syndication.
