Tripodal O‐N‐O Bis‐Phenolato Amine Titanium(IV) Complexes Show High in vitro Anti‐Cancer Activity

Abstract

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 [a]

Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones

“…GI 50 values (concentration required to achieve 50% growth inhibition) were calculated by interpolation, using standard procedures as detailed previously. 6 2.3.3 Cell counts. While MTT assay is commonly used to assess cell viability and proliferation there are several drawbacks to this approach, such as false positive results caused by chemicals that may reduce the MTT (irrespective of any cellular process).…”

“…A total of 10 000 events were recorded for each sample which were counted using a FC500 Beckman Coulter ow cytometer and the results were analysed by using WEASEL. 6 2.3.6 Caspase-3/7 activity assay. Caspase-3/7 activity was determined by Apo-ONE® homogeneous caspase-3/7 assay (Promega).…”

“…4,5 The 4-substituted 2-hydrazinylthiazole species ( 3 ) are attractive, as these are easily prepared from ubiquitous thiosemicarbazones ( 1 ) and low cost α-bromoketones ( 2 ) (Scheme 1). In preliminary studies, associated with another programme, 6 we had incorporated 2-hydrazinylthiazole units into the ligand ( 4 ). To our surprise the exemplar with a 4-cyanophenyl group (alone in the series) showed very high activity against the HCT-116 human colon cancer cell line, while all others had GI 50 values > 100 μM (Scheme 1).…”

“…4,5 The 4-substituted 2-hydrazinylthiazole species (3) are attractive, as these are easily prepared from ubiquitous thiosemicarbazones (1) and low cost a-bromoketones (2) (Scheme 1). In preliminary studies, associated with another programme, 6 we had Scheme 1 Accessing 2-hydrazinylthiazoles (3) and initial hit discovery. incorporated 2-hydrazinylthiazole units into the ligand (4).…”

Titanium complexes bearing 2,6‐bis(o‐hydroxyalkyl)pyridine ligands in vitro cytotoxicity against triple‐negative breast‐cancer cells

“…Therefore, nonplatinum metal complexes have been developed to replace platinum-based complexes. Among these nonplatinum complexes, Ti complexes [3][4][5][6][7][8][9][10][11][12][13][14][15] exhibit considerable antitumor activity as shown in Figure 1.…”