Limits...
Bis-indole derivatives with antitumor activity turn out to be specific ligands of human telomeric G-quadruplex.

Amato J, Iaccarino N, Pagano B, Morigi R, Locatelli A, Leoni A, Rambaldi M, Zizza P, Biroccio A, Novellino E, Randazzo A - Front Chem (2014)

Bottom Line: Bis-indolinone derivatives having either 2,6-disubstituted pyridine core (1a and 1b) or 1,10-disubstituted phenanthroline core (2a and 2b), already known to have antitumor activity, have been tested as potential G-quadruplex binders.Compounds 2a and 2b are able to selectively stabilize G-quadruplex over duplex DNA, and also to discriminate among different G-quadruplex structures, having a particular affinity for the parallel form of the human telomeric G-quadruplex.Both compounds are also able to induce telomeric DNA damage that may explain the activity of these compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, University of Naples "Federico II" Naples, Italy.

ABSTRACT
Bis-indolinone derivatives having either 2,6-disubstituted pyridine core (1a and 1b) or 1,10-disubstituted phenanthroline core (2a and 2b), already known to have antitumor activity, have been tested as potential G-quadruplex binders. Compounds 2a and 2b are able to selectively stabilize G-quadruplex over duplex DNA, and also to discriminate among different G-quadruplex structures, having a particular affinity for the parallel form of the human telomeric G-quadruplex. Both compounds are also able to induce telomeric DNA damage that may explain the activity of these compounds.

No MeSH data available.


Related in: MedlinePlus

Chemical structures. Chemical structures of compounds 1a,b and 2a,b.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4109613&req=5

Figure 1: Chemical structures. Chemical structures of compounds 1a,b and 2a,b.

Mentions: Recently, some of us have synthesized and successfully tested very similar molecules as antitumor agents: the bis-indolinone derivatives with the 2,6-disubstituted pyridine core (1a and 1b) as well as the same derivatives with the 1,10-disubstituted phenanthroline core (2a and 2b) (Figure 1) (Andreani et al., 2008, 2010). Interestingly, the structural similarities of these compounds with the mentioned G4 binders inspired us a further investigation in order to evaluate the G4 binding properties of 1a,b and 2a,b, and possibly to propose a potential mode of action of these derivatives capable to explain their antitumor activity. In particular, in this paper we report the results of the binding studies of compounds 1a,b and 2a,b with different G-quadruplex topologies, along with their capability to induce telomeric damage.


Bis-indole derivatives with antitumor activity turn out to be specific ligands of human telomeric G-quadruplex.

Amato J, Iaccarino N, Pagano B, Morigi R, Locatelli A, Leoni A, Rambaldi M, Zizza P, Biroccio A, Novellino E, Randazzo A - Front Chem (2014)

Chemical structures. Chemical structures of compounds 1a,b and 2a,b.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109613&req=5

Figure 1: Chemical structures. Chemical structures of compounds 1a,b and 2a,b.
Mentions: Recently, some of us have synthesized and successfully tested very similar molecules as antitumor agents: the bis-indolinone derivatives with the 2,6-disubstituted pyridine core (1a and 1b) as well as the same derivatives with the 1,10-disubstituted phenanthroline core (2a and 2b) (Figure 1) (Andreani et al., 2008, 2010). Interestingly, the structural similarities of these compounds with the mentioned G4 binders inspired us a further investigation in order to evaluate the G4 binding properties of 1a,b and 2a,b, and possibly to propose a potential mode of action of these derivatives capable to explain their antitumor activity. In particular, in this paper we report the results of the binding studies of compounds 1a,b and 2a,b with different G-quadruplex topologies, along with their capability to induce telomeric damage.

Bottom Line: Bis-indolinone derivatives having either 2,6-disubstituted pyridine core (1a and 1b) or 1,10-disubstituted phenanthroline core (2a and 2b), already known to have antitumor activity, have been tested as potential G-quadruplex binders.Compounds 2a and 2b are able to selectively stabilize G-quadruplex over duplex DNA, and also to discriminate among different G-quadruplex structures, having a particular affinity for the parallel form of the human telomeric G-quadruplex.Both compounds are also able to induce telomeric DNA damage that may explain the activity of these compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, University of Naples "Federico II" Naples, Italy.

ABSTRACT
Bis-indolinone derivatives having either 2,6-disubstituted pyridine core (1a and 1b) or 1,10-disubstituted phenanthroline core (2a and 2b), already known to have antitumor activity, have been tested as potential G-quadruplex binders. Compounds 2a and 2b are able to selectively stabilize G-quadruplex over duplex DNA, and also to discriminate among different G-quadruplex structures, having a particular affinity for the parallel form of the human telomeric G-quadruplex. Both compounds are also able to induce telomeric DNA damage that may explain the activity of these compounds.

No MeSH data available.


Related in: MedlinePlus