Amine−Guanidine Switch: A Promising Approach to Improve DNA Binding and Antiproliferative Activities

Abstract

A series of polyaromatic guanidino derivatives was synthesized and evaluated for growth inhibitory properties in several human carcinoma cell lines. The properties of these guanidino compounds were compared to those of their corresponding synthetic amino precursors. The size of the polyaromatic ring system as well as the length of the tether attached to the ring had a direct impact on the observed antiproliferative profiles, compound 14 having the broadest spectrum of activity. As both series intercalate DNA, guanidine derivatives showed a remarkable affinity for DNA and the guanidinium group appeared to be essential, yet not sufficient for caspase-3/7 activation. Compound 14 also showed significant in vivo activity against breast cancer cell xenografts in NOG/SCID mice. These results suggest that the electronic nature of chain tethering an intercalator not only influences the DNA-binding process but also controls the antitumoral activity of the whole compound.

Polycyclic aromatic compounds as anticancer agents: Evaluation of synthesis and in vitro cytotoxicity

“…5). This pattern is similar to a previous study (34) showing that a pyrene derivate accumulated in the cytosol of cells. These data suggest that the low level of cytotoxicity observed for these compounds is more likely due to their inability to access nuclear DNA in cells rather than a low binding affinity for DNA, although no studies have been performed to assess the DNA binding affinity of these compounds.…”

“…Previous reports from our group and from other authors have shown that certain derivatives of PAHs, including pyrene and chrysene derivatives, reduce the viability of transformed cell lines (1,20,34), and some of these PAH derivatives have been reported to reduce cell viability by induction of apoptosis (34,35). Therefore, we tested the effects of compounds 1, 2 and 3 on the viability of a small panel of human and mouse cell lines, including liver cancer cell lines (HepG2 and Hepa1-6), colon cancer cell lines (HT-29 and Caco-2), a cervical cancer cell line (HeLa) and NIH3T3 cells.…”

Stability and structural recovery of the tetramerization domain of p53-R337H mutant induced by a designed templating ligand

“…S9). Although 2 also bound to the protein, it displayed considerably lower affinity (37). These results underscored the importance of both hydrophobic and electrostatic contributions, as well as hydrogen bonding in the protein recognition event.…”

Guanidinylation: A simple way to fabricate cell penetrating peptide analogue‐modified chitosan vector for enhanced gene delivery

“…On the other hand, the critical complexing ratio increases as the content of guanidine group is augmented, manifesting guanidinylated chitosan exhibits a weaker binding strength with DNA compared to chitosan. That is because apart from strong electrostatic interaction, part of guanidine groups may form hydrogen bonding interactions with DNA, 26 and this weaker attraction force inevitably reduces the binding ability of GCS with DNA than amines as reported previously. 16 It is well documented that chitosan becomes soluble and can form polyelectrolyte complexes with polyanions as pH is below its pKa, 6.5.…”