Pt(iv) complexes based on cyclohexanediamines and the histone deacetylase inhibitor 2-(2-propynyl)octanoic acid: synthesis, characterization, cell penetration properties and antitumor activity. Issue 13 (16th March 2021)

• Record Type: Journal Article
• Authors: Gabano, Elisabetta; Rangone, Beatrice; Perin, Elena; Caron, Giulia; Ermondi, Giuseppe; Vallaro, Maura; Gandin, Valentina; Marzano, Cristina; Barbanente, Alessandra; Margiotta, Nicola; Ravera, Mauro
• Is Part Of: Dalton transactions. Volume 50:Issue 13(2021)
• Page Start: 4663
• Page End: 4672
• Publication Date: 2021-03-16
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d0dt04135a
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Combinations of different cyclohexanediamines and 2-(2-propynyl)octanoate in Pt(iv ) complexes resulted in prodrug candidates with promising antiproliferative and in vivo antitumor activity. 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-1 R, 2 R -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-1 R, 2 R -diamine and racemic POA ) was tested in vivo on mice bearing Lewis lung carcinoma, showing good tumor growth inhibition with negligible body weight loss.