TY  - JOUR
A1  - Nimbarte, Vijaykumar D.
A1  - Wirmer-Bartoschek, Julia
A1  - Gande, Santosh Lakshmi
A1  - Alshamleh, Islam
A1  - Seibert, Marcel
A1  - Nasiri, Hamid Reza
A1  - Schnütgen, Frank
A1  - Serve, Hubert
A1  - Schwalbe, Harald
T1  - Synthesis and in vitro evaluation of novel 5-nitroindole derivatives as c-Myc G-quadruplex binders with anticancer activity
T2  - ChemMedChem : chemistry enabling drug discovery
N2  - Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biological and biophysical analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5′- and 3′-ends) in a 2 : 1 stoichiometry.
KW  - c-Myc
KW  - G-quadruplex binders
KW  - nitroindoles
KW  - oncogene promoters
KW  - reactive oxygen species
KW  - structure-activity relationships
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62095
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-620957
SN  - 1860-7187
N1  - This work was additionally supported by the Deutsche Forschungsgemeinschaft (SFB1177; SCHN1166/4-1 (to F.S.). Open access funding enabled and organized by Projekt DEAL.
VL  - 16
IS  - 10
SP  - 1667
EP  - 1679
PB  - Wiley-VCH
CY  - Oxford
ER  -