Novel indole-thiazole and indole-thiazolidinone derivatives as DNA groove binders.

International journal of biological macromolecules 2021 Feb 15

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In this study, we report the synthesis of eight novel indole-thiazole and indole-thiazolidinone derivatives, as well as their ability to interact with DNA, analysed through the UV-vis absorption, fluorescence, circular dichroism (CD), viscosity techniques and molecular docking. The ctDNA interaction analysis demonstrated different spectroscopic effects and the affinity constants (Kb) calculated by the UV-vis absorption method were between 2.08 × 105 and 6.99 × 106 M-1, whereas in the fluorescence suppression constants (Ksv) ranged between 0.38 and 0.77 × 104 M-1 and 0.60-7.59 × 104 M-1 using Ethidium Bromide (EB) and 4',6-Diamidino-2-phenylindole (DAPI) as fluorescent probes, respectively. Most derivatives did not alter significantly the secondary structure of the ctDNA according to the CD results. None of the compounds was able to change the relative viscosity of the ctDNA. These results prove that compounds interact with ctDNA via groove binding, which was confirmed by A-T rich oligonucleotide sequence assay with compound JF-252, suggesting the importance of both the phenyl ring coupled to C-4 thiazole ring and the bromo-unsubstituted indole nucleus. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Josival Emanuel Ferreira Alves, Jamerson Ferreira de Oliveira, Tulio Ricardo Couto de Lima Souza, Ricardo Olímpio de Moura, Luiz Bezerra de Carvalho Júnior, Maria do Carmo Alves de Lima, Sinara Mônica Vitalino de Almeida. Novel indole-thiazole and indole-thiazolidinone derivatives as DNA groove binders. International journal of biological macromolecules. 2021 Feb 15;170:622-635