Novel Titanocene Y derivative with albumin affinity exhibits improved anticancer activity against platinum resistant cells.
J Inorg Biochem
; 254: 112520, 2024 05.
Article
in En
| MEDLINE
| ID: mdl-38460481
ABSTRACT
The antitumor activity of Ti(IV)-based compounds put them in the spotlight for cancer treatment in the past, but their lack of stability in vivo due to a high rate of hydrolysis has hindered their development as antitumor drugs. As a possible solution for this problem, we have reported a synthesis strategy through which we combined a titanocene fragment, a tridentate ligand, and a long aliphatic chain. This strategy allowed us to generate a titanium compound (Myr-Ti) capable of interacting with albumin, highly stable in water and with cytotoxic activity in tumor cells[1]. Following a similar strategy, now we report the synthesis of a new compound (Myr-TiY) derived from titanocene Y that shows antitumoral activity in a cisplatin resistant model with a 50% inhibitory concentration (IC50) of 41-76 µM. This new compound shows high stability and a strong interaction with human serum albumin. Myr-TiY has a significant antiproliferative and proapoptotic effect on the tested cancer cells and shows potential tumor selectivity when assayed in non-tumor human epithelial cells being more selective (1.3-3.8 times) for tumor cells than cisplatin. These results lead us to think that the described synthesis strategy could be useful to generate compounds for the treatment of both cisplatin-sensitive and cisplatin-resistant cancers.
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1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organometallic Compounds
/
Neoplasms
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
J Inorg Biochem
Year:
2024
Document type:
Article
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