Differences in electrochemical response of prospective anticancer drugs IPBD and Cl-IPBD, doxorubicin and Vitamin C at plasmid modified glassy carbon

Abstract

For the comparison of the DNA interactions with drugs, two newly synthesized prospective anticancer drugs, 6-(1H-imidazo[4,5-b]phenasine-2-yl)benzene-1,3-diol (IPBD) and, its -Cl derivative (Cl-IPBD) have been compared with doxorubicin, a drug widely used in medicine, and with Vitamin C. These compounds were accumulated at a supercoiled scpUC19 plasmid layer formed on a glassy carbon electrode (GCE). Stability of the drug-plasmid/GCE layer was achieved by initial plasmid accumulation using prolonged potential cycling for ca. 200 min. from highly diluted scpUC19 solutions (8 pg/mL), followed by accumulation of the drugs from 1 µM - 50 µM. Electrochemical properties in terms of the redox potentials of the compounds and capacitative/resistive characteristics of the layers have been tested using, in sequence, four voltammetric methods: Square Wave (SWV), Differential Pulse (DPV) and Alternating Current (ACV) with phase detection 0° and 90°. Importantly, with progressive drug accumulation in the plasmid, for Cl-IPBD, but not for IPBD, an increase in peak (I) at -0.42 V vs. SCE was observed, while biological tests revealed a higher cytotoxic activity for Cl-IPBD vs. IPBD. Moreover, an additional redox signal of Cl-IPBD was observed with the compound reductive accumulation at the plasmid layer in the presence of Vitamin C.

Keywords: 6-(1H-imidazo[4,5-b]phenasine-2-yl)benzene-1,3-diol (IPBD); Anticancer drugs; DNA supercoiled plasmid scpUC19; Vitamin C.