Transition metal complexes have continued to constitute an appealing class of medicinal compounds since the exceptional discovery of cisplatin in the late 1960s. Pt(II)-based complexes are endowed with a broad range of biological properties, which are mainly exerted by targeting DNA. In this study, we report a significant biological investigation into and computation analyses of four Pt(II)-complexes, namely, LDP-1–4, synthesized and characterized according to previously reported procedures. Molecular-modelling studies highlighted that the top two LDP compounds (i.e., LDP-1 and LDP-4) might bind to both matched and mismatched base pair sites of the oligonucleotide 5′-(dCGGAAATTACCG)2-3′, supporting their anticancer potential. These two complexes displayed noteworthy cytotoxicity in vitro (sub-micromolar–micromolar range) against two leukaemia cell lines, i.e., CCRF-CEM and its multi-drug-resistant counterpart CEM/ADR5000, and remarkable anti-angiogenic properties (in the sub-micromolar range) evaluated in an in vivo model, i.e., a chick embryo chorioallantoic membrane (CAM) assay.

Antileukemia Activity and Mechanism of Platinum(II)-Based Metal Complexes

Maria Letizia Di Pietro
Primo
;
Claudio Stagno
Secondo
;
Valeria D’Angelo;Maria Paola Germanò;Anna Cacciola;Federica De Gaetano;Nunzio Iraci
Penultimo
;
Nicola Micale
Ultimo
2022-01-01

Abstract

Transition metal complexes have continued to constitute an appealing class of medicinal compounds since the exceptional discovery of cisplatin in the late 1960s. Pt(II)-based complexes are endowed with a broad range of biological properties, which are mainly exerted by targeting DNA. In this study, we report a significant biological investigation into and computation analyses of four Pt(II)-complexes, namely, LDP-1–4, synthesized and characterized according to previously reported procedures. Molecular-modelling studies highlighted that the top two LDP compounds (i.e., LDP-1 and LDP-4) might bind to both matched and mismatched base pair sites of the oligonucleotide 5′-(dCGGAAATTACCG)2-3′, supporting their anticancer potential. These two complexes displayed noteworthy cytotoxicity in vitro (sub-micromolar–micromolar range) against two leukaemia cell lines, i.e., CCRF-CEM and its multi-drug-resistant counterpart CEM/ADR5000, and remarkable anti-angiogenic properties (in the sub-micromolar range) evaluated in an in vivo model, i.e., a chick embryo chorioallantoic membrane (CAM) assay.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3248144
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