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Metal NHC Complexes with Naphthalimide Ligands as DNA‐Interacting Antiproliferative Agents
Author(s) -
Streciwilk Wojciech,
Terenzi Alessio,
Misgeld Rainer,
Frias Corazon,
Jones Peter G.,
Prokop Aram,
Keppler Bernhard K.,
Ott Ingo
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600557
Subject(s) - chemistry , circular dichroism , moiety , carbene , ruthenium , stereochemistry , rhodium , dna , intercalation (chemistry) , metal , combinatorial chemistry , biochemistry , catalysis , organic chemistry
Naphthalimide‐based N ‐heterocyclic carbene (NHC) complexes of the type [(1,5‐cyclooctadiene)(NHC)RhCl)] ( 4 a – c ), [( p ‐cymene)(NHC)RuCl 2 )] ( 5 a – c ), and [(NHC)CuBr] ( 6 a – c ) were synthesized and investigated as antiproliferative agents that target DNA. The cytotoxic effects were largely driven by the naphthalimide structure, which is a DNA‐intercalating moiety. Regarding the metal center, the highest activities were observed with the rhodium complexes, and cytotoxic activity was significantly lower for the ruthenium derivatives. The stable coordination of the NHC ligands of selected complexes 4 b and 5 b in solution was confirmed, and their DNA binding properties were studied by UV/Vis spectroscopy, mass spectrometry, and circular dichroism. Stable intercalative binding into the DNA for all selected naphthalimide‐based complexes is indicated by high DNA binding constants. Particularly efficient binding was observed in the case of the rhodium complex 4 b . More detailed biological studies on 4 b showed promising activities against multidrug‐resistant Nalm‐6 cells and confirmed an important role for mitochondrial pathways in 4 b ‐induced apoptosis.