We present the synthesis and characterization of novel square planar transition metal complexes of Schiff base ligands,which act as guanine quadruplex binders and stabilizers.The complexes stabilize quadruplexes relat...We present the synthesis and characterization of novel square planar transition metal complexes of Schiff base ligands,which act as guanine quadruplex binders and stabilizers.The complexes stabilize quadruplexes related to telomere stability or present in oncogene regulatory sequences,as determined by optical spectroscopy,pointing out the emergence of selectivity towards specific structures or sequences.These results are supported and rationalized by molecular modeling simulations.Furthermore,we show that the treatment of cancer cell lines with our complexes is associated with the increase in the number of nuclear guanine quadruplexes and the downregulation in the expression of the considered oncogenes.Remarkably,only very moderate cytotoxicity can be observed for all complexes.These results pave the way for the development of selective anticancer treatment by metal compounds targeting the expression of specific oncogenes.展开更多
基金support of this work through Labex SEAM ANR 11 LABEX 086,ANR 11 IDEX 0502The authors thank Prof A.Palumbo Piccionello,University of Palermo,for his support with mass spectrometry,and Prof C.Kowol and Dr W.Kandioller,University of Vienna,and Dr Y.Bernhard,L2CM-UMR CNRS 7053,University of Lorraine,for their support with elemental analysis+1 种基金The support of the IdEx“Universite Paris 2019”ANR-18-IDEX-0001 is also acknowledgedThe financial support of the European Union-NextGenerationEU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 Project PE_00000019“HEAL ITALIA”CUP(B73C22001250006)is gratefully acknowledged.
文摘We present the synthesis and characterization of novel square planar transition metal complexes of Schiff base ligands,which act as guanine quadruplex binders and stabilizers.The complexes stabilize quadruplexes related to telomere stability or present in oncogene regulatory sequences,as determined by optical spectroscopy,pointing out the emergence of selectivity towards specific structures or sequences.These results are supported and rationalized by molecular modeling simulations.Furthermore,we show that the treatment of cancer cell lines with our complexes is associated with the increase in the number of nuclear guanine quadruplexes and the downregulation in the expression of the considered oncogenes.Remarkably,only very moderate cytotoxicity can be observed for all complexes.These results pave the way for the development of selective anticancer treatment by metal compounds targeting the expression of specific oncogenes.
