Synthesis and evaluation of novel amphiphilic conjugates of FDA approved non-steroidal anti-inflammatory drugs as potential antimicrobial against drug resistant pathogens
Implementing Organization
Principal Investigator
Dr. Rikeshwer Prasad Dewangan
Jamia Hamdard, Delhi
CO-Principal Investigator
Dr. Mairaj Ahmed Ansari
Jamia Hamdard, Delhi-110062
About
Antimicrobial resistance (AMR) is a growing global concern due to overprescription and irrational use of antibiotics. ESKAPE pathogens, including Enterobacter species, are the leading cause of nosocomial infections worldwide. These pathogens are multidrug resistant (MDR) isolates, making antibiotics ineffective in treating infections. To address this issue, new antimicrobial agents with novel modes of action are needed. Non-steroidal anti-inflammatory drugs (NSAIDs) are highly prescribed as analgesics and anti-inflammatory drugs. However, their mild to moderate activity limits their repurposing for clinical applications. A study aims to modify rationally selected NSAIDs with bio-vector molecules spermine to create amphiphiles, which can potentiate their antibacterial action for membrane targeting and intracellular modes of action. Preliminary studies have been conducted, and results are inspiring further research. More analogues will be synthesized for structural optimization and evaluated for antimicrobial action against gram positive and gram negative bacterial strains, including clinically relevant MDR pathogens. The proposed molecules mimic host defense antimicrobial peptides, with irresistible modes of action, such as permeabilization of the cell envelope through open pores, which prevent bacterial resistance. The presence of NSAID moiety in the proposed amphiphiles makes them therapeutically viable drug-like molecules.