Original scientific paper
https://doi.org/10.15255/KUI.2023.013
DNA Binding Affinity Assessment of Xanthene Compounds: In Vitro and In Silico Approach
Elma Veljović
orcid.org/0000-0003-1129-1491
; University of Sarajevo-Faculty of Pharmacy, Zmaja od Bosne 8, 71 000 Sarajevo, Bosnia and Herzegovina
Amar Osmanović
orcid.org/0000-0002-4206-6177
; University of Sarajevo-Faculty of Pharmacy, Zmaja od Bosne 8, 71 000 Sarajevo, Bosnia and Herzegovina
Mirsada Salihović
orcid.org/0000-0001-7497-4084
; University of Sarajevo-Faculty of Pharmacy, Zmaja od Bosne 8, 71 000 Sarajevo, Bosnia and Herzegovina
Nevzeta Ljubijankić
; University of Sarajevo-Faculty of Science, Zmaja od Bosne 33-35, Sarajevo 71 000, Bosnia and Herzegovina
Sabina Begić
orcid.org/0000-0002-3523-8268
; University of Sarajevo-Faculty of Science, Zmaja od Bosne 33-35, Sarajevo 71 000, Bosnia and Herzegovina
Selma Špirtović-Halilović
; University of Sarajevo-Faculty of Pharmacy, Zmaja od Bosne 8, 71 000 Sarajevo, Bosnia and Herzegovina
Abstract
Xanthene derivatives are an important class of heterocyclic compounds with a wide spectrum of pharmacological activities. In our previous investigations, we found the good antiproliferative activity of two xanthene derivatives, with minimal toxicity investigated by in vitro tests. In this study, we tested the interaction of compound 1 (powerful potent antiproliferative compound) with calf thymus DNA (CT-DNA) under physiological conditions by spectrophotometric titration. The probable prediction of binding and the type of interaction forces involved in the arrangement between xanthene derivatives and CT-DNA were explored also through molecular docking studies.
The results indicated that compound 1 interacts with CT-DNA by grove binding. The binding constant was found to be 2.5 ∙ 104 M–1 indicating the non-covalent binding of compound 1 to CT-DNA. Docking study results proposed possible binding modes, with binding energies of −9.39 and −8.65 kcal mol–1 for compounds 1 and 2, respectively, which supported previously obtained in vitro results for antiproliferative activity.
In addition to experimental investigation, density functional theory (DFT) calculation with B3LYP/6-31G*, B3LYP/6-31G**, and B3LYP/6-31+G* levels of theories was performed on compounds 1 and 2 to obtain optimised geometry, spectroscopic and electronic properties.
These studies could help in understanding the mechanisms of toxicity, resistance, side effects of xanthene derivatives, and their binding action mechanism to DNA.
Keywords
DNA binding; docking; DFT; xanthene
Hrčak ID:
309708
URI
Publication date:
11.11.2023.
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