Enhanced G-Quadruplex DNA Stabilization and Telomerase Inhibition by Novel Fluorescein Derived Salen and Salphen Based Ni(II) and Pd(II) Complexes.
Metal based salen complexes have been considered as an important scaffold toward targeting of DNA structures. In the present work, we have synthesized nickel(II) and palladium(II) salen and salphen complexes by using readily available fluorescein as the backbone to provide an extended aromatic surface. The metal complexes exhibit affinity toward the human telomeric G-quadruplex DNA with promising inhibition of telomerase activity. This has been ascertained by their efficiency in the long term cell proliferation assay which showed significant cancer cell toxicity in the presence of the metal complexes. Confocal microscopy showed cellular internalization followed by localization in the nucleus and mitochondria. Considerable population at the sub-G1 phase of the cell cycle showed cell death via apoptotic pathway.
Asfa
A
Ali
Mohini
M
Kamra
Soma
S
Roy
K
K
Muniyappa
Director's Research Unit, Indian Association for the Cultivation of Science , Kolkata 700 032, India.
Santanu
0000-0001-9040-8971
S
Bhattacharya
D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005029:Ethylenediamines / Q000737:chemistry; D019793:Fluorescein / Q000737:chemistry*; D054856:G-Quadruplexes / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D009532:Nickel / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry*; D010655:Phenylenediamines / Q000737:chemistry; D019098:Telomerase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D005029:Ethylenediamines; D009942:Organometallic Compounds; D010655:Phenylenediamines; C545695:salphen; D010165:Palladium; D009532:Nickel; D004247:DNA; C011452:disalicylaldehyde ethylenediamine; D019098:Telomerase; D019793:Fluorescein