Development of New Benzothiazole Derivatives as Potential OFF-ON Fluorescent Probes for Quantification of Duplex DNA

Development of New Benzothiazole Derivatives as Potential OFF-ON Fluorescent Probes for Quantification of Duplex DNA

• Author
• Esaú Marques Brandão
• Co-authors
• Kadja Luana Chagas Monteiro , Thiago Mendonça de Aquino , Edeildo Ferreira da Silva-Júnio , Josué Carinhanha Caldas Santos
• Abstract

• ABSTRACT

   

  INTRODUCTION: In recent years, there has been a surge of interest in small organic molecules possessing fluorescent properties upon interaction with specific analytes¹. Various mechanisms underlie the fluorescence exhibited by probes, with the "off-on" (or "turn-on") mechanism being a notable one. In this mechanism, the probe demonstrates minimal or no fluorescence when in its free form (the "off" state), but upon interaction with a target biomolecule, a significant increase in fluorescence intensity occurs (the "on" state)². Notably, probes derived from benzothiazole derivatives have displayed promising outcomes in monitoring the formation of protein fibrils, which are implicated in neurodegenerative diseases, and in interacting with DNA, resulting in enhanced fluorescence emission¹,³,?. Benzothiazole-based compounds possess two crucial attributes that render them potential fluorescent probes with biological applications: (i) an affinity for DNA and (ii) substantial electronic delocalization along their molecular framework.

  AIMS: This study presents the synthesis of novel benzothiazole derivatives designed as potential spectroscopic probes for DNA quantification, capitalizing on the "off-on" concept.

  METHODS: To synthesize the target compounds, the initial step involved the reaction of 2-methyl benzothiazole with methyl bromide. Subsequently, this N-Methylated intermediate was condensed with the requisite aldehydes to obtain the final compounds. The structures of all compounds were confirmed through 1H and 13C nuclear magnetic resonance (NMR) spectroscopy.

  RESULTS AND DISCUSSION: Eight distinct compounds, with yields ranging from 60% to 90%, were successfully synthesized. The NMR spectra of all compounds corroborated the expected structures.

  CONCLUSION: The synthesis and purification procedures employed in the production of these compounds proved effective, yielding eight molecules with satisfactory yields and without significant challenges in the purification process. As a future perspective, all derivatives will be subjected to comprehensive evaluation regarding their interaction with DNA, with the aim of further applications as fluorescent probes.

  KEYWORDS: Fluorescent Probe; Benzothiazole; DNA Quantification.

  REFERENCES:

  1. MURUDKAR, S., et al. Ultrafast molecular rotor: an efficient sensor for premelting of natural DNA. Chemical Communications. Índia, v. 48, p. 5301-5303. Mar., 2012.

  2. TABUCHI, Y.; TAKI, M. Fluorescent “keep-on” type pharmacophore obtained from dynamic combinatorial library of Schiff bases. Analytical and Bioanalytica Chemistry, v. 410, n. 26, p. 6713–6717, 2018.

  3. SINGH, P. K., et al. Probing the DNA–ionic liquid interaction using an ultrafast molecular rotor. Journal of Photochemistry and Photobiology A: Chemistry, Índia, v. 246, p. 16-22, Out., 2012.

   

  4. LIU, L. et al. Selective recognition of ds-DNA cavities by a molecular rotor: switched fluorescence of thioflavin T. Molecular Biosystems, China, v. 9, p. 2512-2517, Jul., 201

• Keywords
• Fluorescent Probe; Benzothiazole; DNA Quantification.
• Modality
• Pôster
• Subject Area
• Drug Design and Discovery, Synthesis and Natural Products