Cytotoxicity and DNA interaction in a series of aryl terminated iminopyridine Pt(II) complexes

被引:3
作者
Bondi, Riccardo [1 ]
Dalla Via, Lisa [2 ,3 ]
Hyeraci, Mariafrancesca [3 ]
Pagot, Gioele [4 ]
Labella, Luca [1 ,2 ]
Marchetti, Fabio [1 ]
Samaritani, Simona [1 ,2 ]
机构
[1] Univ Pisa, Dipartimento Chim & Chim Ind, Via Giuseppe Moruzzi 13, I-56124 Pisa, Italy
[2] Consorzio Interuniv Ric Chim Metalli Sistemi Biol, Bari, Italy
[3] Univ Padua, Dipartimento Sci Farmaco, Via F Marzolo 5, I-35131 Padua, Italy
[4] Univ Padua, Dipartimento Ingn Ind, Via F Marzolo 9, I-35131 Padua, Italy
关键词
Iminopyridine platinum(II) complexes; Antiproliferative properties; Cisplatin resistance; DNA interaction; Groove binding; Intercalation; INTERSTRAND CROSS-LINKS; OVARIAN-CANCER CELLS; PLATINUM(II) COMPLEXES; CISPLATIN RESISTANCE; BEARING PYRIDINECARBOXALDIMINES; ADDUCT FORMATION; REPAIR; POLYMERIZATION; PALLADIUM(II); DERIVATIVES;
D O I
10.1016/j.jinorgbio.2020.111335
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A series of iminopyridine complexes of platinum(II), bearing a flexible diethereal, aryl terminated residue, where the size of aryl group is varied from phenyl to 9-anthracenyl, was synthesized. The new complexes are soluble and stable in DMSO/H2O mixtures. Besides the metal center, aryl groups are available for further interactions with DNA, due to the good side chain flexibility. The new aryl functionalized iminopyridine dichlorido platinum (II) complexes show a significant antiproliferative activity on ovarian carcinoma cells and notably, complex 13 is able to overcome cisplatin resistance. The study of the interaction mode of 13 with DNA highlighted the ability to form a molecular complex characterized by a dual (intercalative and groove binding) geometry. The complex is also able to covalently add to DNA even though interstrand cross-links appear significantly hampered with respect to cisplatin. The interactions with the macromolecule are discussed in view of the observed cell effect.
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页数:9
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