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

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.

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-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.

New quinoline-arylamidine hybrids: Synthesis, DNA/RNA binding and antitumor activity.

Four series of new hybrid molecules with 7-chloroquinoline and arylamidine moieties joined through the rigid -O- (groups I (2a-g) and II (5a-g)) or flexible -NH-CH-CH-O- (groups III (8a-g) and IV (10a-g)) linker were synthesized, and their DNA/RNA binding properties and cytotoxic activity were tested, against several human cancer lines. The compounds and their interaction with DNA and RNA were studied by UV-Vis and CD spectroscopy. The obtained results showed that the binding affinity of the investigated compounds increases proportionally with the increase of the length and number of groups able to form hydrogen bonds with ds-polynucleotides.

An Aromatic Diamidine That Targets Kinetoplast DNA, Impairs the Cell Cycle in Trypanosoma cruzi, and Diminishes Trypomastigote Release from Infected Mammalian Host Cells.

Trypanosoma cruzi is the etiological agent of Chagas disease, affecting approximately 10 million people in the Americas and with some 40 million people at risk. The objective of this study was to evaluate the anti-T. cruzi activity of three new diamidines that have a 3,4-ethylenedioxy extension of the thiophene core, designated MB17, MB19, and MB38.

Mechanistic investigation of charge-remote and charge-driven fragmentation processes in 2,5-diphenyl-3,4-ethylenedioxythiophene diamidines.

Rationale: Diphenylfuran diamidines represent an important class of DNA minor groove binders of high therapeutic interest as antitumor and antibacterial agents. This study aimed to investigate fragmentation patterns in mass spectra of four diamidine derivatives with significant antitumor activity, in order to gain more insight into the structures and stability of their putative biological metabolites.

Methods: Compounds were investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS) using low-energy collision-induced dissociation (CID).