br mol This happens due to
mol −1. This happens due to 7ESTAC01's ability to form an H-bond with the NH donor from the TAK242 base (DA18), at a distance of 2.836 Å (Fig. 5B). After DFT calculations from ctDNA and 7ESTAC01 (free and binding), Gibbs free energy (ΔG) from the complex was low, suggesting a high affinity, showing its relation to the FitScore value, 63.44 (Table S). Therefore, binding of 7ESTAC01 analyzed via molecular docking (Fig. 5C), demonstrates that this compound could act via intercalation mechanism, considering that the aminothiophene and partially acridine rings are located between the DNA bases.
A careful analysis of the type of interaction between the hybrid 7ESTAC01 and the DNA represents the success of producing oxidative damage in the DNA. In this way, the interaction between DNA and 7ESTAC01 characterized by UV–Vis spectroscopy, Molecular Docking, and DFT studies showed that the 7ESTAC01 act via an intercalation mechanism into the DNA. Besides, the low free energy of Gibbs (ΔG) calculated from molecular docking suggests an excellent affinity 7ESTAC01-DNA.
Here, a novel electrochemical biosensor, divided into two config-urations, SL-DNA/GE and dsDNA/GE, was optimized and characterized
for detection of DNA damage caused by intercalation with a new hybrid anti-cancer drug (7ESTAC01). DPV analysis of guanine and adenine bases presented high sensitivity and efficiency of the SL-DNA probe modified GE and the dsDNA. High intercalation between DNA and 7ESTAC01 was determined to be a critical parameter to improve the sensitivity of the biosensor. DPV analysis of dsDNA in the presence of high concentration of 7ESTAC01 led to the formation of 8-oxoguanine, which is considered a key indicator of a mutagenic lesion in DNA. Intercalation mechanism was demonstrated using molecular docking, DFT studies, and UV–Vis Spectroscopy. These studies showed ami-nothiophene and partially acridine rings located between DNA bases, as well as an isosbestic point at 297 nm in the 7ESTAC01-DNA spectra, indicating the intercalation as a dominant binding mode.
The dsDNA/GE showed higher sensitivity in the presence of the 7ESTAC01 due to a higher quantity of purine bases in comparison to the SL-DNA by itself. The high sensitivity of this novel biosensor allows detection of minimal DNA damage and can be further expanded to study DNA damage with many other drugs.
Optimization of SL-DNA/GE and dsDNA/GE biosensor by Cyclic Voltammetry, electrochemical ctDNA biosensor on the Glassy Carbon Electrode, Detection of the DNA damage product of the interaction of ctDNA/GCE and 7ESTAC01, DPV signal of 7ESTAC01 on the Gold Electrode, Molecular Docking and DFT studies for 7ESTAC01 and calf thymus DNA. This material is ginkgos available free of charge via the Internet.
K. Lozano Untiveros, et al.
CRediT authorship contribution statement
Katherine Lozano Untiveros: Conceptualization, Methodology, Validation, Investigation, Writing - original draft, Writing - review & editing. Emanuella Gomes da Silva: Methodology, Writing - review & editing. Fabiane Caxico de Abreu: Conceptualization, Validation, Investigation, Writing - review & editing, Supervision, Funding acqui-sition. Edeildo Ferreira da Silva-Júnior: Methodology. João Xavier de Araújo-Junior: Methodology. Thiago Mendoça de Aquino: Methodology, Writing - review & editing, Supervision, Funding acqui-sition. Stephanie M. Armas: Validation, Investigation, Writing - review
& editing. Ricardo Olímpio de Moura: Methodology. Francisco J.B. Mendonça-Junior: Methodology, Writing - review & editing. Vanessa Lima Serafim: Methodology. Karin Chumbimuni-Torres: Conceptualization, Validation, Investigation, Writing - review & editing, Supervision, Funding acquisition.
This work is supported by Organization of American States (OAS) under the OAS-GCUB scholarship program (P.202.458.3000). Foundation for Research Support of the State Alagoas (FAPEAL), Brazil. NSF-CBET, United States, grant number #1706802 and Florida Department of Health Grant #7ZK05.
Declaration of interests
Appendix A. Supporting information
168 Accepted Manuscript
Title: AN EVALUATION OF THE SUITABILITY, READABILITY, QUALITY, AND USEFULNESS OF ONLINE RESOURCES FOR FAMILY CAREGIVERS OF PATIENTS WITH CANCER
Authors: Olivia Monton, Sylvie Lambert, Eric Belzile, Dahlal Mohr-Elzeki
To appear in:
Patient Education and Counseling
Please cite this article as: Monton O, Lambert S, Belzile E, Mohr-Elzeki
D, AN EVALUATION OF THE SUITABILITY, READABILITY, QUALITY, AND USEFULNESS OF ONLINE RESOURCES FOR FAMILY CAREGIVERS OF PATIENTS WITH CANCER, Patient Education and Counseling (2019), https://doi.org/10.1016/j.pec.2019.05.010