<i>N</i>-Heterocyclic Carbene-Platinum Complexes Featuring an Anthracenyl Moiety: Anti-Cancer Activity and DNA Interaction

• Main Authors: Sébastien Harlepp, Edith Chardon, Mathilde Bouché, Georges Dahm, Mounir Maaloum, Stéphane Bellemin-Laponnaz
• Format: Article
• Language: English
• Published: MDPI AG 2019-08-01
• Series: International Journal of Molecular Sciences
• Subjects: antitumoral activity; platinum; N-heterocyclic carbene; two-state interaction; AFM and optical tweezers microscopy
• Online Access: https://www.mdpi.com/1422-0067/20/17/4198

A platinum (II) complex stabilized by a pyridine and an N-heterocyclic carbene ligand featuring an anthracenyl moiety was prepared. The compound was fully characterized and its molecular structure was determined by single-crystal X-ray diffraction. The compound demonstrated high in vitro antiproliferative activities against cancer cell lines with IC₅₀ ranging from 10 to 80 nM. The presence of the anthracenyl moiety on the N-heterocyclic carbene (NHC) Pt complex was used as a luminescent tag to probe the metal interaction with the nucleobases of the DNA through a pyridine-nucleobase ligand exchange. Such interaction of the platinum complex with DNA was corroborated by optical tweezers techniques and liquid phase atomic force microscopy (AFM). The results revealed a two-state interaction between the platinum complex and the DNA strands. This two-state behavior was quantified from the different experiments due to contour length variations. At 24 h incubation, the stretching curves revealed multiple structural breakages, and AFM imaging revealed a highly compact and dense structure of platinum complexes bridging the DNA strands.