Tools
Tools
Musa, M, Abid, M, Bradshaw, TD, Boocock, DJ 
ORCID: https://orcid.org/0000-0002-7333-3549, Coveney, C ORCID: https://orcid.org/0000-0001-7047-6408, Argent, SP and Woodward, S,
2024.
Probing the mechanism of action of bis(phenolato) amine (ONO donor set) titanium(IV) anticancer agents.
Journal of Medicinal Chemistry, 67 (4), pp. 2732-2744.
ISSN 0022-2623
Preview |
Text
2277765_Boocock.pdf - Published version Download (3MB) | Preview |
Abstract
The need for anticancer therapies that overcome metallodrug resistance while minimizing adverse toxicities is targeted, herein, using titanium coordination complexes. Octahedral titanium(IV) trans,mer-[Ti{R1N(CH2–2-MeO-4-R1-C6H2)2}2] [R1 = Et, allyl, n-Pr, CHO, F, CH2(morpholino), the latter from the formyl derivative; R2 = Me, Et; not all combinations] are attained from Mannich reactions of commercial 2-methoxyphenols (27–74% overall yield, 2 steps). These crystalline (four X-ray structures) Ti(IV)-complexes are active against MCF-7, HCT-116, HT-29, PANC-1, and MDA-MB-468 cancer cell lines (GI50 = 0.5–38 μM). Their activity and cancer selectivity (vs nontumor MRC-5 cells) typically exceeds that of cisplatin (up to 16-fold). Proteomic analysis (in MCF-7) supported by other studies (G2/M cell cycle arrest, ROS generation, γH2AX production, caspase activation, annexin positivity, western blot, and kinase screens in MCF-7 and HCT-116) suggest apoptosis elicited by more than one mechanism of action. Comparison of these data to the modes of action proposed for salan Ti(IV) complexes is made.
| Item Type: | Journal article |
|---|---|
| Publication Title: | Journal of Medicinal Chemistry |
| Creators: | Musa, M., Abid, M., Bradshaw, T.D., Boocock, D.J., Coveney, C., Argent, S.P. and Woodward, S. |
| Publisher: | American Chemical Society (ACS) |
| Date: | 22 February 2024 |
| Volume: | 67 |
| Number: | 4 |
| ISSN: | 0022-2623 |
| Identifiers: | Number Type 10.1021/acs.jmedchem.3c01874 DOI 2277765 Other |
| Rights: | © 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/). |
| Divisions: | Schools > School of Science and Technology |
| Record created by: | Laura Ward |
| Date Added: | 04 Dec 2024 09:19 |
| Last Modified: | 04 Dec 2024 09:19 |
| URI: | https://irep.ntu.ac.uk/id/eprint/52692 |
Actions (login required)
 |
Edit View |
Statistics
Views
Views per month over past year
Downloads
Downloads per month over past year
