Unveiling interactions between DNA and cytotoxic 2-arylpiperidinyl-1,4-naphthoquinone derivatives: A combined electrochemical and computational study

• Main Authors: Christian Espinosa-Bustos, Camila Canales, Galo Ramírez, Pablo Jaque, Cristian O. Salas
• Format: Article
• Language: English
• Published: Elsevier 2020-01-01
• Series: Arabian Journal of Chemistry
• Online Access: http://www.sciencedirect.com/science/article/pii/S1878535218300893

Three 2-arylpiperidinyl-1,4-naphthoquinone derivatives were synthesized and evaluated in vitro to determine their cytotoxicity on cancer and normal cell lines. In order to establish their possible action mechanism, the electrochemical behaviour of these quinones was examined using cyclic voltammetry (CV) as technique by using a three-electrode setup: a glassy carbon, Ag/AgCl (in 3 M KCl), and platinum wire as working, reference, and counter electrodes, respectively. Kinetic studies were done to determine the control of the reduction reaction and the number of transferred electrons in the process. Furthermore, the addition of dsDNA to the quinone solutions allowed for the observation of an interaction between each quinone and dsDNA as the current-peaks became lower in presence of dsDNA. Otherwise, motivated to support the aforementioned results, electronic structure calculations at the TPSS-D3/6-31+G(d,p) level of theory were carried out in order to find the most favourable noncovalently bonded complexes between quinones and DNA. Noncovalent complexes formed between DNA and 2-arylpiperidinyl-1,4-naphthoquinones and stabilized by π-stacking interactions along with the well-known hydrogen-bonded complexes were found, with the former being more stable than the latter. These results suggest that the intercalation of these quinone derivatives in DNA is the most likely action mechanism. Keywords: Naphthoquinone derivatives, Cytotoxicity, DNA interaction, Electrochemistry, Computational study