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β ‐Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding
Author(s) -
Lord Rianne M.,
Mannion James J.,
Crossley Benjamin D.,
Hebden Andrew J.,
McMullon Max W.,
Fisher Julie,
Phillips Roger M.,
McGowan Patrick C.
Publication year - 2016
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201601290
Subject(s) - octahedron , ligand (biochemistry) , dna , chemistry , titanium , cytotoxicity , stereochemistry , cisplatin , in vitro , crystallography , heptane , crystal structure , receptor , organic chemistry , biochemistry , biology , chemotherapy , genetics
Herein, we report 30 new β ‐diketonate titanium compounds of the type [Ti( O,O ) 2 X 2 ], whereby O,O =asymmetric or symmetric β ‐diketonate ligand and X=Cl, Br, OEt or O i Pr. Thirteen new crystal structures are discussed and show that these octahedral species all adopt cis geometries in the solid state. These compounds have been tested for their cytotoxicity using SRB and MTT assays, showing several of the compounds are as potent as cisplatin against a range of tumor cell lines. Results also show the [Ti( O,O ) 2 Br 2 ] complexes are more potent than [Ti( O,O ) 2 Cl 2 ], [Ti( O,O ) 2 (OEt) 2 ] and [Ti( O,O ) 2 (O i Pr) 2 ]. Using a simple symmetrical heptane‐3,5‐dione ( O,O ) ligand bound to titanium, we observed more than a 50‐fold increase in potency with the [Ti( O,O ) 2 Br 2 ] ( 28 ) when compared to [Ti( O,O ) 2 Cl 2 ] ( 27 ). One of the more potent compounds ( 6 ) has been added to three different sixmers of DNA, in order to analyse the potential DNA binding of the compound. NMR studies have been carried out on the compounds, in order to understand the structural properties and the species formed in solution during the in vitro cell assays.