Pt(iv) complexes based on cyclohexanediamines and the histone deacetylase inhibitor 2-(2-propynyl)octanoic acid: synthesis, characterization, cell penetration properties and antitumor activity.
Dalton Trans
; 50(13): 4663-4672, 2021 Apr 07.
Article
in En
| MEDLINE
| ID: mdl-33725031
ABSTRACT
The Pt(iv) complexes based on (SP-4-2)-dichlorido(cyclohexane-1,4-diamine)platinum(ii) (kiteplatin) and the histone deacetylase inhibitor 2-(2-propynyl)octanoic acid (POA) were investigated. Since POA contains a chiral carbon, all the possible Pt(iv) isomers were prepared and characterized, and their antiproliferative activity on six cancer cell lines was compared with that of the corresponding Pt(iv) complexes containing the cyclohexane-1R,2R-diamine equatorial ligand. To justify the very good antiproliferative activity (nanomolar IC50), the polarity, lipophilicity, permeability, and cell accumulation of the complexes were studied. Overall, the two series of Pt(iv) complexes showed similar cell penetration properties, being significantly better than that of the Pt(ii) reference compounds. Finally, a representative compound of the whole set of complexes (i.e., that based on cyclohexane-1R,2R-diamine and racemic POA) was tested in vivo on mice bearing Lewis lung carcinoma, showing good tumor growth inhibition with negligible body weight loss.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organoplatinum Compounds
/
Histone Deacetylase Inhibitors
/
Histone Deacetylases
/
Antineoplastic Agents
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Dalton Trans
Journal subject:
QUIMICA
Year:
2021
Type:
Article
Affiliation country:
Italy