March 03, 2016
The UK College of Pharmacy Research Publication Highlight for February, 2016 is titled “Synthesis and Bioactivities of Kanamycin B-Derived Cationic Amphiphiles” and was published in the Journal of Medicinal Chemistry.
The study was conducted in the UK College of Pharmacy’s division of Medicinal, Bioorganic, and Computational Chemistry in the Pharmaceutical Sciences department. The study was led by two postdoctoral scholars; Marina Fosso, PhD and Sanjib Shrestha, PhD being an equal contributors under Dr. Sylvie Garneau-Tsodikova, PhD supervision. Staff scientist Keith Green, PhD also contributed to the work. .
Antibiotic resistance is a growing world health concern, causing leaders at the National Institutes of Health, the World Health Organization, and others to sound alarms that antibiotics used in the treatment of infectious diseases may soon be ineffective. Thus, there is an immediate and critical need for the development of new and better antibiotics. This month’s Research Highlight features a manuscript that describes the synthesis of two new compounds with enhanced antimicrobial activity. The investigators began with Kanamycin B, a close cousin to Kanamycin A and minor component in Kanamycin formulations used in the treatment of a wide range of bacterial and fungal infections. The investigators added hydrophobic residues to the aminoglycoside backbone of Kanamycin B to create a series of cationic amphiphiles, positively charged compounds with both hydrophilic and hydrophobic properties. Two of these compounds exhibited antibacterial and antifungal activity. Importantly, both compounds were resistant to enzymes used by bacteria to detoxify aminoglycoside antibiotics. Neither compound was toxic to human cells at concentrations needed for antimicrobial activity, suggesting they may be useful in the treatment of infections. More importantly, these novel amphiphilic aminoglycosides exhibited synergistic antifungal effect with medically used antifungal agents (azoles) that open up the way for possible new antifungal strategies against human and animal fungal diseases.
“This is a great first-step in the potential development of new drugs for the treatment of antibiotic resistant infections.” said Greg Graf, Assistant Dean for Translational Research.