Multicationic amphiphiles
Transcript of Multicationic amphiphiles
Multicationic amphiphiles: Novel Antiseptic and Biofilm disrupting agents
Pooja Majmudar, PhDTechnology Commercialization ManagerTemple University1801 N. Broad StreetConwell Hall, RM 401APhiladelphia, PA 19122Office Phone: 215-204-2660Email: [email protected] www.temple.edu/research/otdc
Inventor:
William M. Wuest, PhD.Department Of ChemistryTemple University, Philadelphia, PA
Background
• A growing number of medical infections are caused by bacteria, parasites, viruses and fungi that are resistant to antibiotics.
• Every year more than 2 million people in the US get antibiotic-resistant infections and at least 23,000 die because current drugs no longer have the ability to stop their infections (CDC).
• There is a shortage of antimicrobial agents in the pharmaceutical industry pipeline.
• Over 80 % of all infections are associated with biofilms in which their resistance to currently available antibiotics increases and their capability for evading many host defenses enhances.
• Biofilm infections lead to chronic/persistent infections or disabilities which contributes to an extremely heavy burden to overall healthcare costs.
Overview
Biscationic or Triscationic amphiphile
Simple and low cost preparation
method
Antimicrobial agent, able to Kill
and inhibit growth of
microorganisms
Amphiphiles
• Served as antimicrobial agents for centuries• Common amphiphilic substances are soaps, detergents and lipoproteins.
• Cationic amphiphiles are membrane disruptors, capitalizing on electrostatic interactions with the anionic bacterial cell membrane.
Active antiseptic in Lysol® (benzylalkonium chloride)
Multicationic Amphiphiles
Quaternary ammonium Amphiphiles
bis-pyridinium structures
TMEDA core
All-carbon core
Preparation of biscationic amphiphiles
Preparation and structures of mono- bis- and tris- quaternary ammonium cations
Biofilms
• Biofilm infections cause over 65% of nosocomial and foreign device infections (CDC).
These compounds possess minimum biofilm eradication concentrations as low as 25 µM against Gram-positive biofilms, making them the most active anti-biofilm structures reported to date.
Applications
• Killing or inhibiting the growth of microorganisms including but not limited to bacteria, viruses, yeast, fungi, protozoa
• Killing or dispersing pre-established bacterial biofilms
• Cleaning and Sterilization
• Treatment of wounds, diseases or infections
• Antiseptics, oil-pipeline cleaning, and antifouling treatment for ships
Advantages
Low cost
Simple Production
Ability to disrupt established Biofilms
Broad range of activity
Demand
• During the past five years, growing consumer awareness of health, hygiene and the impact of pathogens worldwide has spurred growth in demand for disinfectants.
• Hospitals and other healthcare service providers use disinfectants to control infectious organisms.
Market for Disinfectants
Related publications by the inventor
• Black, Jacob W., Megan C. Jennings, Julianne Azarewicz, Thomas J. Paniak, Melissa C. Grenier, William M. Wuest, and Kevin PC Minbiole. "TMEDA-derived biscationic amphiphiles: An economical preparation of potent antibacterial agents." Bioorganic & medicinal chemistry letters 24, no. 1 (2014): 99-102.
• Jennings, Megan C., Laura E. Ator, Thomas J. Paniak, Kevin PC Minbiole, and William M. Wuest. "Biofilm Eradicating Properties of Quaternary Ammonium Amphiphiles: Simple ‐Mimics of Antimicrobial Peptides." ChemBioChem 15, no. 15 (2014): 2211-2215.
• Ator, Laura E., Megan C. Jennings, Amanda R. McGettigan, Jared J. Paul, William M. Wuest, and Kevin PC Minbiole. "Beyond paraquats: Dialkyl 3, 3 -and 3, 4 -bipyridinium amphiphiles as ′ ′antibacterial agents." Bioorganic & medicinal chemistry letters 24, no. 16 (2014): 3706-3709.
• Fletcher, Madison H., Megan C. Jennings, and William M. Wuest. "Draining the moat: disrupting bacterial biofilms with natural products." Tetrahedron 70, no. 37 (2014): 6373-6383.