TY - JOUR
T1 - Pt(iv) complexes based on cyclohexanediamines and the histone deacetylase inhibitor 2-(2-propynyl)octanoic acid
T2 - synthesis, characterization, cell penetration properties and antitumor activity
AU - Gabano, Elisabetta
AU - Rangone, Beatrice
AU - Perin, Elena
AU - Caron, Giulia
AU - Ermondi, Giuseppe
AU - Vallaro, Maura
AU - Gandin, Valentina
AU - Marzano, Cristina
AU - Barbanente, Alessandra
AU - Margiotta, Nicola
AU - Ravera, Mauro
N1 - Publisher Copyright:
© The Royal Society of Chemistry 2021.
PY - 2021/4/7
Y1 - 2021/4/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85103697705&partnerID=8YFLogxK
U2 - 10.1039/d0dt04135a
DO - 10.1039/d0dt04135a
M3 - Article
SN - 1477-9226
VL - 50
SP - 4663
EP - 4672
JO - Dalton Transactions
JF - Dalton Transactions
IS - 13
ER -