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

Amidinobenzimidazole derivatives connected to 1-aryl-substituted 1,2,3-triazole through phenoxymethylene linkers 7a-7e, 8a-8e, and 9a-9e were designed and synthesised with the aim of evaluating their anti-bacterial and anti-trypanosomal activities and DNA/RNA binding affinity. Results from anti-bact...

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Published in:Journal of enzyme inhibition and medicinal chemistry 2018-01, Vol.33 (1), p.1323-1334
Main Authors: Bistrović, Andrea, Krstulović, Luka, Stolić, Ivana, Drenjančević, Domagoj, Talapko, Jasminka, Taylor, Martin C., Kelly, John M., Bajić, Miroslav, Raić-Malić, Silvana
Format: Article
Language:English
Subjects:
1,2,3-triazole
antiprotozoal activity
Benzimidazole
MRSA
Research Paper
resistant bacteria
Trypanosoma brucei
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Summary:Amidinobenzimidazole derivatives connected to 1-aryl-substituted 1,2,3-triazole through phenoxymethylene linkers 7a-7e, 8a-8e, and 9a-9e were designed and synthesised 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 towards 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.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2018.1484733