Naslov
Diaryltriazenes as Antibacterial Agents Against Methicillin Resistant Staphylococcus aureus (MRSA) and Mycobacterium smegmatis

Autori
Vajs, Jure ; Proud, Conor ; Brozović, Anamaria ; Gazvoda, Martin ; Lloyd, Adrian ; Roper, David ; Osmak, Maja ; Košmrlj, Janez ; Dowson, Christopher

Izvornik
European journal of medicinal chemistry (0223-5234) 127 (2017); 223-234

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Antibacterial agents ; Methicillin resistant Staphylococcus aureus (MRSA) ; Mycobacterium smegmatis ; Antibiotic resistance ; Triazenes

Sažetak
Diaryltriazene derivatives were synthesized and evaluated for their antimicrobial properties. Initial experiments showed some of these compounds to have activity against both methicillin-resistant strains of Staphylococus aureus (MRSA) and Mycobacterium smegmatis, with MICs of 0.02 and 0.03 μg/mL respectively. Those compounds with potent anti-staphylococcal and anti-mycobacterial activity were not found to act as growth inhibitors of mammalian cell lines or yeast. Furthermore, we demonstrated that one of the most active anti-MRSA diaryltriazene derivatives was subject to very low frequencies of resistance at <10−9. Whole genome sequencing of resistant isolates identified mutations in the enzyme that lysylates phospholipids. This could result in the modification of phospholipid metabolism and consequently the characteristics of the staphylococcal cell membrane, ultimately modifying the sensitivity of these pathogens to triazene challenge. Our work has therefore extended the potential range of triazenes, which could yield novel antimicrobials with low levels of resistance.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA