Molecular mechanism of action of new 1,4-naphthoquinones tethered to 1,2,3-1H-triazoles with cytotoxic and selective effect against oral squamous cell carcinoma

Chipoline, Ingrid C.; Fonseca, Anna Carolina Carvalho da; Costa, Gabriella Ribeiro Machado da; Souza, Michele Pereira de; Rabelo, Vitor Won‐Held; Queiroz, Lucas Nicolau de; Souza, Theo Luiz Ferraz de; Almeida, Elan Cardozo Paes de; Abreu, Paula Alvarez; Pontes, Bruno; Ferreira, Vı́tor F.; Silva, Fernando de Carvalho da; Robbs, Bruno Kaufmann

doi:10.1016/j.bioorg.2020.103984

Cited by 21 publications

(8 citation statements)

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“…This result shows that the compound is capable of inhibiting the production of clones from a single cell, it also shows the cellular response to treatment in a longer evaluation period, in which the cells were maintained in a viable condition of growth [ 38 ]. Chipoline and colleagues [ 39 ] observed in their study with 1,4-naphthoquinone derivatives that naphthoquinone compounds are able to reduce the formation of oral squamous cell carcinoma colonies (SSC-9), without reducing the viability of non-cells fibroblast tumor cells. Caro and colleagues [ 40 ] also observed that the naphthoquinone derivative 8-hydroxy-2-(2-tenoyl)naphtho[2,3- b ] thiophene-4,9-dione reduced the formation of human colorectal adenocarcinoma cell colonies (HT-29).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies demonstrate using different analyzes that naphthoquinone derivatives show cytotoxic activity in tumor cells through the induction of apoptosis [ 32 , 45 ]. Chipoline and colleagues [ 39 ] observed that an 1,4-naphthoquinone derivative analyzed in their research induced apoptosis in SCC-9 cells (oral squamous cell carcinoma). The main changes observed were cell morphology alterations with disorganization of microtubules and inhibition of topoisomerase [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Chipoline and colleagues [ 39 ] observed that an 1,4-naphthoquinone derivative analyzed in their research induced apoptosis in SCC-9 cells (oral squamous cell carcinoma). The main changes observed were cell morphology alterations with disorganization of microtubules and inhibition of topoisomerase [ 39 ]. The topoisomerase enzyme is responsible for breaking and repairing DNA strands [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

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Anti-proliferative and pro-apoptotic activity of glycosidic derivatives of lawsone in melanoma cancer cell

et al. 2021

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Background Melanoma is a malignant cancer that affects melanocytes and is considered the most aggressive skin-type cancer. The prevalence for melanoma cancer for the last five year is about one million cases. The impact caused of this and other types of cancer, revel the importance of research into potential active compounds. The natural products are an important source of compounds with biological activity and research with natural products may enable the discovery of compounds with potential activity in tumor cells. Methods The Sulforhodamine B was used to determine cell density after treatment with lawsone derivatives. Apoptosis and necrosis were analyzed by flow cytometer. Morphological changes were observed by fluorescence using the Phalloidin/FITC and DAPI stains. The clonogenic and wound healing assays were used to analyze reduction of colonies formation and migratory capacity of melanoma cells, respectability. Results In pharmacological screening, seven compounds derived from lawsone were considered to have high cytotoxic activity (GI > 75%). Three compounds were selected to assess the inhibitory concentration for 50% of cells (IC50), and the compound 9, that has IC50 5.3 μM in melanoma cells, was selected for further analyses in this cell line. The clonogenic assay showed that the compound is capable of reducing the formation of melanoma colonies at 10.6 μM concentration. The compound induced apoptotic morphological changes in melanoma cells and increased by 50% the cells dying from apoptosis. Also, this compound reduced the migratory capacity of melanoma cells. Conclusions The results of this study showed that the evaluated lawsone derivatives have potential activity on tumor cells. The compound 9 is capable of inducing cell death by apoptosis in melanoma cells (B16F10).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Anti-proliferative and pro-apoptotic activity of glycosidic derivatives of lawsone in melanoma cancer cell

et al. 2021

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“…Quinones are known to cause microtubule disarrangement and to induce the formation of reactive oxygen species (ROS), damaging the cell membranes and the DNA (clastogenicity); the latter is also damaged by the inhibition, caused by 1,4-NQ, of the human topoimerase IIα enzyme, an enzyme responsible for maintaining the DNA topology [11,33,34,[37][38][39]. Complementary to the formation of ROS, quinones are known to have inflammatory potential, by upregulating inflammatory genes such as IL-6, IL-8, TNF-α, Cyp1a1 and HO-1 [40].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Toxicity on Lung Cells of By-Products Present in Naphthalene Secondary Organic Aerosols

Albuquerque

Berger

Tomaz

et al. 2021

Life

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In 2018, seven million people died prematurely due to exposure to pollution. Polycyclic aromatic hydrocarbons (PAHs) are a significant source of secondary organic aerosol (SOA) in urban areas. We investigated the toxic effects of by-products of naphthalene SOA on lung cells. These by-products were 1,4-naphthoquinone (1,4-NQ), 2-hydroxy-1,4-naphthoquinone (2-OH-NQ), phthalic acid (PA) and phthaldialdehyde (OPA). Two different assessment methodologies were used to monitor the toxic effects: real-time cell analysis (RTCA) and the Holomonitor, a quantitative phase contrast microscope. The chemicals were tested in concentrations of 12.5 to 100 µM for 1,4-NQ and 1 to 10 mM for 2-OH-NQ, PA and OPA. We found that 1,4-NQ is toxic to cells from 25 to 100 µM (EC50: 38.7 µM ± 5.2); 2-OH-NQ is toxic from 1 to 10mM (EC50: 5.3 mM ± 0.6); PA is toxic from 5 to 10 mM (EC50: 5.2 mM ± 0.3) and OPA is toxic from 2.5 to 10 mM (EC50: 4.2 mM ± 0.5). Only 1,4-NQ and OPA affected cell parameters (migration, motility, motility speed and optical volume). Furthermore, 1,4-NQ is the most toxic by-product of naphthalene, with an EC50 value that was one hundred times higher than those of the other compounds. RTCA and Holomonitor analysis showed a complementarity when studying the toxicity induced by chemicals.

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“…Dificultando ainda mais, em geral, menos de 0,01 % dos protótipos de compostos bioativos sintetizados nos laboratórios têm sucesso nas etapas préclínicas, que compreendem os ensaios biológicos in vitro realizados após a etapa de síntese, purificação e caracterização. [1][2][3][4][5] Dentro deste contexto, sintetizar compostos contendo um núcleo 1,2,3-triazólico em sua estrutura molecular (1-13) é uma estratégia eficiente e amplamente explorada [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] para obtenção de novas moléculas com variadas atividades biológicas, como: antiviral [26][27][28][29] , antídoto 30,31 , antiinflamatória 32 , antibacteriana 33 , antitumoral 34,35 e antimicrobiana 36 (Figura 2). Dentre as vantagens de se incorporar este heterociclo, de origem estritamente sintética, na estrutura molecular do produto planejado destacam-se: (i) podem interagir com diferentes receptores biológicos através de ligações de hidrogênio e/ou interações hidrofóbicas do tipo π-stacking com resíduos de aminoácidos como a fenilalanina; (ii) podem atuar como elos de união entre duas moléculas (linkers), possibilitando a obtenção de compostos híbridos; (iii) podem ser introduzidos na estrutura molecular de um composto como um bioisóstero, por exemplo, na substituição de uma função amida, a fim de evitar reações de hidrólise.…”

Section: Introductionunclassified

1,2,3-Triazole Nucleus as a Versatile Tool for the Obtainment of Novel Biologically Active Compounds: an Overview

Lessa¹

2021

Rev. Virtual Quim.

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Molecular mechanism of action of new 1,4-naphthoquinones tethered to 1,2,3-1H-triazoles with cytotoxic and selective effect against oral squamous cell carcinoma

Cited by 21 publications

References 43 publications

Anti-proliferative and pro-apoptotic activity of glycosidic derivatives of lawsone in melanoma cancer cell

Anti-proliferative and pro-apoptotic activity of glycosidic derivatives of lawsone in melanoma cancer cell

Evaluation of the Toxicity on Lung Cells of By-Products Present in Naphthalene Secondary Organic Aerosols

1,2,3-Triazole Nucleus as a Versatile Tool for the Obtainment of Novel Biologically Active Compounds: an Overview

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