Novel symmetric bis-benzimidazoles: Synthesis, DNA/RNA binding and antitrypanosomal activity.

Abstract

The novel benzimidazol-2-yl-fur-5-yl-(1,2,3)-triazolyl dimeric series with aliphatic and aromatic central linkers was successfully prepared with the aim of assessing binding affinity to DNA/RNA and antitrypanosomal activity. UV-Visible spectroscopy, thermal denaturation showed interaction of heterocyclic bis-amidines with ctDNA. Circular dichroism studies indicated uniform orientation of heterocyclic bis-amidines along the chiral double helix axis, revealing minor groove binding as the dominant binding mode. The amidino fragment and 1,4-bis(oxymethylene)phenyl spacer were the main determinants of activity against Trypanosoma brucei. The bis-benzimidazole imidazoline 15c, which had antitrypanosomal potency in the submicromolar range and DNA interacting properties, emerged as a candidate for further structural optimization to obtain more effective agents to combat trypanosome infections.

• Authors: A Bistrović Popov, I Stolić, L Krstulović, M C Taylor, J M Kelly, S Tomić, L Tumir, M Bajić, S Raić-Malić
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 173 Pg. 63-75 (Jul 01 2019) ISSN: 1768-3254 [Electronic] France
• PMID: 30986572 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Chemical References

• Benzimidazoles
• Trypanocidal Agents
• bis-benzimidazole

Topics

• Benzimidazoles (chemical synthesis, chemistry, pharmacology)
• Binding Sites (drug effects)
• Dose-Response Relationship, Drug
• Molecular Structure
• Parasitic Sensitivity Tests
• Structure-Activity Relationship
• Trypanocidal Agents (chemical synthesis, chemistry, pharmacology)
• Trypanosoma brucei brucei (drug effects)