Naphth[1,2-]imidazoles Bioactive from β-Lapachone: Fluorescent Probes and Cytotoxic Agents to Cancer Cells

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Apr 13

PMID 37049771

Authors

Victoria Laysna Dos Anjos Santos

Arlan de Assis Gonsalves

Delis Galvao Guimaraes

Sidney Silva Simplicio

Helinando Pequeno de Oliveira

Lara Polyana Silva Ramos

Marcilia Pinheiro da Costa

Fatima de Cassia Evangelista de Oliveira

Claudia Pessoa

Cleonia Roberta Melo Araujo

Affiliations

Soon will be listed here.

Abstract

Theranostics combines therapeutic and imaging diagnostic techniques that are extremely dependent on the action of imaging agent, transporter of therapeutic molecules, and specific target ligand, in which fluorescent probes can act as diagnostic agents. In particular, naphthoimidazoles are potential bioactive heterocycle compounds to be used in several biomedical applications. With this aim, a group of seven naphth[1,2-]imidazole compounds were synthesized from β-lapachone. Their optical properties and their cytotoxic activity against cancer cells and their compounds were evaluated and confirmed promising values for molar absorptivity coefficients (on the order of 10 to 10), intense fluorescence emissions in the blue region, and large Stokes shifts (20-103 nm). Furthermore, the probes were also selective for analyzed cancer cells (leukemic cells (HL-60). The naphth[1,2-]imidazoles showed IC between 8.71 and 29.92 μM against HL-60 cells. For HCT-116 cells, values for IC between 21.12 and 62.11 μM were observed. The selective cytotoxicity towards cancer cells and the fluorescence of the synthesized naphth[1,2-]imidazoles are promising responses that make possible the application of these components in antitumor theranostic systems.

References

Moura K, Carneiro P, Pinto M, da Silva J, Malta V, De Simone C . 1,3-Azoles from ortho-naphthoquinones: synthesis of aryl substituted imidazoles and oxazoles and their potent activity against Mycobacterium tuberculosis. Bioorg Med Chem. 2012; 20(21):6482-8. DOI: 10.1016/j.bmc.2012.08.041. View

Araneda J, Piers W, Heyne B, Parvez M, McDonald R . High Stokes shift anilido-pyridine boron difluoride dyes. Angew Chem Int Ed Engl. 2011; 50(51):12214-7. DOI: 10.1002/anie.201105228. View

Gerber D, Beg M, Fattah F, Frankel A, Fatunde O, Arriaga Y . Phase 1 study of ARQ 761, a β-lapachone analogue that promotes NQO1-mediated programmed cancer cell necrosis. Br J Cancer. 2018; 119(8):928-936. PMC: 6203852. DOI: 10.1038/s41416-018-0278-4. View

Pena-Moran O, Villarreal M, Alvarez-Berber L, Meneses-Acosta A, Rodriguez-Lopez V . Cytotoxicity, Post-Treatment Recovery, and Selectivity Analysis of Naturally Occurring Podophyllotoxins from Bursera fagaroides var. fagaroides on Breast Cancer Cell Lines. Molecules. 2016; 21(8). PMC: 6274026. DOI: 10.3390/molecules21081013. View

Wu X, Sun X, Guo Z, Tang J, Shen Y, James T . In vivo and in situ tracking cancer chemotherapy by highly photostable NIR fluorescent theranostic prodrug. J Am Chem Soc. 2014; 136(9):3579-88. DOI: 10.1021/ja412380j. View

Bombaca A, Silva L, Augusto Chaves O, da Silva L, Barbosa J, da Silva A . Novel N,N-di-alkylnaphthoimidazolium derivative of β-lapachone impaired Trypanosoma cruzi mitochondrial electron transport system. Biomed Pharmacother. 2021; 135:111186. DOI: 10.1016/j.biopha.2020.111186. View

Costa D, Pereira Rangel L, Martins-Dinis M, Diniz da Silva Ferretti G, Ferreira V, Silva J . Anticancer Potential of Resveratrol, β-Lapachone and Their Analogues. Molecules. 2020; 25(4). PMC: 7070981. DOI: 10.3390/molecules25040893. View

Kelkar S, Reineke T . Theranostics: combining imaging and therapy. Bioconjug Chem. 2011; 22(10):1879-903. DOI: 10.1021/bc200151q. View

Zhang J, Chen R, Zhu Z, Adachi C, Zhang X, Lee C . Highly Stable Near-Infrared Fluorescent Organic Nanoparticles with a Large Stokes Shift for Noninvasive Long-Term Cellular Imaging. ACS Appl Mater Interfaces. 2015; 7(47):26266-74. DOI: 10.1021/acsami.5b08539. View

10.

Moon D, Kang C, Kim M, Jeon Y, Lee J, Choi Y . Beta-lapachone (LAPA) decreases cell viability and telomerase activity in leukemia cells: suppression of telomerase activity by LAPA. J Med Food. 2010; 13(3):481-8. DOI: 10.1089/jmf.2008.1219. View

11.

Wu I, Yu J, Ye F, Rong Y, Gallina M, Fujimoto B . Squaraine-based polymer dots with narrow, bright near-infrared fluorescence for biological applications. J Am Chem Soc. 2014; 137(1):173-8. PMC: 4304448. DOI: 10.1021/ja5123045. View

12.

Gomez Castellanos J, Prieto J, Heinrich M . Red Lapacho (Tabebuia impetiginosa)--a global ethnopharmacological commodity?. J Ethnopharmacol. 2008; 121(1):1-13. DOI: 10.1016/j.jep.2008.10.004. View

13.

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

14.

Shcherbakova D, Hink M, Joosen L, Gadella T, Verkhusha V . An orange fluorescent protein with a large Stokes shift for single-excitation multicolor FCCS and FRET imaging. J Am Chem Soc. 2012; 134(18):7913-23. PMC: 3348967. DOI: 10.1021/ja3018972. View

15.

Xiao S, Tang Y, Lv Z, Lin Y, Chen L . Nanomedicine - advantages for their use in rheumatoid arthritis theranostics. J Control Release. 2019; 316:302-316. DOI: 10.1016/j.jconrel.2019.11.008. View

16.

Farahat A, Kumar A, Say M, Wenzler T, Brun R, Paul A . Exploration of DAPI analogues: Synthesis, antitrypanosomal activity, DNA binding and fluorescence properties. Eur J Med Chem. 2017; 128:70-78. PMC: 5341734. DOI: 10.1016/j.ejmech.2017.01.037. View

17.

Rezende L, Vaidergorn M, Moraes J, da Silva Emery F . Synthesis, photophysical properties and solvatochromism of meso-substituted tetramethyl BODIPY dyes. J Fluoresc. 2013; 24(1):257-66. DOI: 10.1007/s10895-013-1293-8. View

18.

Telegin F, Marfin Y . New insights into quantifying the solvatochromism of BODIPY based fluorescent probes. Spectrochim Acta A Mol Biomol Spectrosc. 2021; 255:119683. DOI: 10.1016/j.saa.2021.119683. View

19.

Chipem F, Mishra A, Krishnamoorthy G . The role of hydrogen bonding in excited state intramolecular charge transfer. Phys Chem Chem Phys. 2012; 14(25):8775-90. DOI: 10.1039/c2cp23879a. View

20.

Cole J, Holland N . Multifunctional nanoparticles for use in theranostic applications. Drug Deliv Transl Res. 2015; 5(3):295-309. DOI: 10.1007/s13346-015-0218-2. View