Pt(iv) complexes based on cyclohexanediamines and the histone deacetylase inhibitor 2-(2-propynyl)octanoic acid: synthesis, characterization, cell penetration properties and antitumor activity

Elisabetta Gabano, Beatrice Rangone, Elena Perin, Giulia Caron, Giuseppe Ermondi, Maura Vallaro, Valentina Gandin, Cristina Marzano, Alessandra Barbanente, Nicola Margiotta, Mauro Ravera

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

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.

Lingua originaleInglese
pagine (da-a)4663-4672
Numero di pagine10
RivistaDalton Transactions
Volume50
Numero di pubblicazione13
DOI
Stato di pubblicazionePubblicato - 7 apr 2021

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