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Tripodal O‐N‐O Bis ‐Phenolato Amine Titanium(IV) Complexes Show High in vitro Anti‐Cancer Activity
Author(s) -
Abid Mohammed,
Nouch Ryan,
Bradshaw Tracey D.,
Lewis William,
Woodward Simon
Publication year - 2019
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201900510
Subject(s) - chemistry , cisplatin , amine gas treating , titanium , stereochemistry , apoptosis , octahedron , annexin , cell culture , cancer cell , medicinal chemistry , crystallography , crystal structure , cancer , biochemistry , organic chemistry , medicine , surgery , chemotherapy , genetics , biology
The octahedral titanium(IV) complexes trans , mer ‐[Ti{R 3 N(CH 2 C 6 H 2 ‐2‐O‐4‐R 2 ‐6‐R 1 ) 2 } 2 ] (R 1 = Me, OMe, Cl; R 2 = Me, OMe, F, Cl; R 3 = Me, Et; not all combinations) are synthesised in two steps from simple phenols in 36–53 % overall yield. The highly crystalline (4 X‐ray structures) complexes are active against MCF‐7 (breast) and HCT‐116 (colon) cancer cell lines showing widely varying GI 50 values in the range 1–100 µM depending on R 1 –R 3 . Highest activities are realised when R 1 = OMe and R 2 , R 3 = Me (GI 50 ca. 1 µM for MCF‐7 and 2–3 µM for HCT‐116). These are respectively 8× and 3× times greater than the activities of cisplatin in the same cell lines. These titanium complexes show some significant selectivity for cancer cell lines; up to 7× higher in MCF‐7 compared to non‐cancer (MRC‐5) fibroblast cells. Details of cellular mode of action indicators (cell cycle perturbation, Annexin V, γ‐H2AX, and caspase studies) that point to an apoptosis mode for the most active compound (R 1 = OMe and R 2 , R 3 = Me) are also reported.