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

Abstract

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.

Homology Modelling and Molecular Docking Studies of Selected Substituted Benzo[d]imidazol-1-yl)methyl)benzimidamide Scaffolds on Plasmodium falciparum Adenylosuccinate Lyase Receptor

“…Benzimidazole derivatives (substituted benzo[ d ]imidazol-1-yl)methyl)benzimidamides) were considered as potential analogues for AICAR due to similarities in chemical structure (Figure 1), and could be evaluated for their antimalarial propensity. Benzimidazole derivatives have been widely used in recent years due to their wide range of pharmacological activities including antimalarial, 8 antileishmanial, 9 analgesics, 10 anticancer, 11 antitumour, 12 antimicrobial, 13 anti-inflammatory, 14 antihepatitis C virus, 15 antihelmintic, 16 antibacterial 17 and antitrypanosomal 18 activities. Although several benzimidazole derivatives have been synthesised and developed into commercially available drugs, little is known about the design of the template as an inhibitor against P falciparum ADSL ( Pf ADSL).…”

Synthesis, Characterization, and Antiproliferative Activity Studies of Novel Benzimidazole‐Imidazopyridine Hybrids as DNA Groove Binders

“…The value of the intrinsic binding constant K b for compounds 1 and 2 were derived to be 0.4 (± 0.06) × 10 5 M −1 and 1.5 (± 0.3) × 10 5 M −1 , respectively. These values are weaker or comparable to those of the other benzimidazole compounds …”

“…Minor groove binders DAPI and Hoechst33258 were also studied against our compounds. The compounds 1 and 2 did not compete with DAPI but, 2 at high concentrations decreased the Hoechst33258‐DNA complex fluorescence intensity suggesting the minor groove binding mode with weaker affinity similar to other 2‐substituted benzimidazoles …”

“…Presence of benzimidazole moiety and various substitutents around it have provided a wide spectrum of biological activities such as anticoagulants, anti‐inflammatory, antioxidants, proton pump inhibitors, hormone modulators, immunomodulators, antimicrobials, antivirals, antiparasites, anticancer, anti‐hypertensives, CNS stimulants as well as depressants, lipid level modulators, antidiabetics, etc. have created indispensable examples for development of new therapeutic agents . A great number of 2‐substituted benzimidazoles have been synthesized and their biological activities reported (Figure ) .…”

A Novel Ruthenium Based Coordination Compound Against Pathogenic Bacteria

“…Some studies suggest the metal center of the ruthenium binds to the biological target and the metal center of the coordination compound possess antimicrobial activity with biological targets [44], or the metal center of coordination compound which acts as active ligands carrier, normally-established drugs, to enhance their pharmaceutical activities via temporary coordination with the metal moiety [45]. Benzimidazole also has high DNA binding affinity [46]. From the previous studies, we can hypothesize that Schiff base interacts with the bacterial cell wall and make a path for the compound internalization and then the ruthenium core and benzimidazole both act with DNA, or block any enzymatic activity as well.…”