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. SincePOAcontains 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 racemicPOA) was testedin vivoon mice bearing Lewis lung carcinoma, showing good tumor growth inhibition with negligible body weight loss.
Pt(iv) complexes based on cyclohexanediamines and the histone deacetylase inhibitor 2-(2-propynyl)octanoic acid: synthesis, characterization, cell penetration properties and antitumor activity
Gabano E.;Rangone B.;Perin E.;Ermondi G.;Ravera M.
2021-01-01
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. SincePOAcontains 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 racemicPOA) was testedin vivoon mice bearing Lewis lung carcinoma, showing good tumor growth inhibition with negligible body weight loss.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
