Naslov
Synthesis, anti-bacterial and anti-protozoal activities of amidinobenzimidazole derivatives and their interactions with DNA and RNA

Autori
Bistrović, Andrea ; Krstulović, Luka ; Stolić, Ivana ; Drenjančević, Domagoj ; Talapko, Jasminka ; Taylor, Martin C. ; Kelly, John M. ; Bajić, Miroslav ; Raić-Malić, Silvana

Izvornik
Journal of enzyme inhibition and medicinal chemistry (1475-6366) 33 (2018), 1; 1323-1334

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

Ključne riječi
benzimidazole ; 1, 2, 3-triazole ; resistant bacteria ; antiprotozoal activity ; Trypanosoma brucei ; MRSA

Sažetak
Amidinobenzimidazole derivatives connected to 1- aryl-substituted 1, 2, 3-triazole through phenoxymethylene linkers 7a–7e, 8a–8e and 9a–9e were designed and synthesized with the aim of evaluating their anti-bacterial and anti- trypanosomal activities and DNA/RNA binding affinity. Results from anti-bacterial evaluations of antibiotic resistant pathogenic bacteria revealed that both o-chlorophenyl-1, 2, 3-triazole and N-isopropylamidine moieties in 8c led to strong inhibitory activity against resistant Gram- positive bacteria, particularly the MRSA strain. Furthermore, the non-substituted amidine and phenyl ring in 7a induced a marked anti-bacterial effect, with potency against ESBL-producing Gram- negative E. coli better than those of the antibiotics ceftazidime and ciprofloxacin. UV-Vis and CD spectroscopy, as well as thermal denaturation assays, indicated that compounds 7a and 8c showed also binding affinities toward ctDNA Anti-trypanosomal evaluations showed that the p- methoxyphenyl-1, 2, 3-triazole moiety in 7b and 9b enhanced inhibitory activity against T. brucei, with 8b being more potent than nifurtimox, and having minimal toxicity towards mammalian cells.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA