Targeting pathogenic fungi, bacteria and fungal-bacterial biofilms by newly synthesized quaternary ammonium derivative of pyridoxine and terbinafine with dual action profile

Many pathogenic bacteria and microscopic fungi form rigid polymicrobial biofilms this way enhancing their resistant to treatment. A series of novel pyridoxine-based quaternary ammonium derivatives of terbinafine characterized by both Antifungal and Antibacterial activities was designed. The leading compound named KFU-127 exhibits promising Antifungal and Antibacterial activities against various bacteria and micromycetes in both planktonic and biofilm-embedded forms demonstrating MIC values comparable with those of conventional antifungals and antimicrobials. Similar to Other antiseptics like benzalkonium chloride and miramistin, KFU-127 is considerably toxic for eukaryotic cells that limits is application to topical treatment options. On the Other hand, KFU-127 reduces the number of viable biofilm-embedded bacteria and C. albicans by 3 orders of magnitude at concentrations 2-4 times lower than those of reference drugs and successfully eradicates S. aureus-C. albicans mixed biofilms. The mechanism of antimicrobial action of KFU-127 is bimodal including both membrane integrity damage and pyridoxal-dependent Enzymes targeting. We expect that this bilateral mechanism would result in lower rates of resistance development in both Fungal and Bacterial pathogens. Taken together, our data suggest KFU-127 as a new promising broad spectrum topical antimicrobial capable of one-shot targeting of Bacterial and fungal-bacterial biofilms.