Identification of Novel Telomeric G-Quadruplex-Targeting Chemical Scaffolds Through Screening of Three NCI Libraries

TY - JOUR

T1 - Identification of Novel Telomeric G-Quadruplex-Targeting Chemical Scaffolds Through Screening of Three NCI Libraries

AU - Rahman, Khondaker

AU - Tizkova, K

AU - Reszka, AP

AU - Neidle, S

AU - Thurston, David E

PY - 2012

Y1 - 2012

N2 - Thirteen compounds with diverse chemical structures have been identified as selective telomeric G-quadruplex-binding ligands through screening the NCI Diversity Set II, the NCI Natural Products Set II and the NCI Mechanistic Diversity Set libraries containing a total of 2307 members against a human telomeric G-quadruplex using a FRET-based DNA melting assay. These compounds show significant selectivity towards a telomeric G-quadruplex compared to duplex DNA, fall within a molecular weight range of 327-533, and are generally consistent with the Lipinski Rule of Five for drug-likeness. Thus they provide new chemical scaffolds for the development of novel classes of G-quadruplex-targeting agents.

AB - Thirteen compounds with diverse chemical structures have been identified as selective telomeric G-quadruplex-binding ligands through screening the NCI Diversity Set II, the NCI Natural Products Set II and the NCI Mechanistic Diversity Set libraries containing a total of 2307 members against a human telomeric G-quadruplex using a FRET-based DNA melting assay. These compounds show significant selectivity towards a telomeric G-quadruplex compared to duplex DNA, fall within a molecular weight range of 327-533, and are generally consistent with the Lipinski Rule of Five for drug-likeness. Thus they provide new chemical scaffolds for the development of novel classes of G-quadruplex-targeting agents.

U2 - 10.1016/j.bmcl.2012.02.020

DO - 10.1016/j.bmcl.2012.02.020

M3 - Article

SN - 0960-894X

VL - 22

SP - 3006

EP - 3010

JO - BIOORGANIC AND MEDICINAL CHEMISTRY LETTERS

JF - BIOORGANIC AND MEDICINAL CHEMISTRY LETTERS

IS - 8

ER -