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Abstract Background Lung cancer is the deadliest type of cancer in the world and the search for compounds that can treat this disease is highly important. Lawsone (2-hydroxy-1,4-naphtoquinone) is a naphthoquinone found in plants from the Lawsone genus that show a high cytotoxic effect in cancer cell lines and its derivatives show an even higher cytotoxic effect. Methods Sulforhodamine B was used to evaluate the cytotoxic activity of compounds on tumor cells. Clonogenic assay was used to analyze the reduction of colonies and wound healing assay to the migratory capacity of A549 cells. Apoptosis and necrosis were analyzed by flow cytometer and Giemsa staining. Hemolysis assay to determine toxicity in human erythrocytes. Results Lawsone derivatives were evaluated and compound 1 (O-propargyllawsone) was the one with the highest cytotoxic effect, with IC50 below 2.5 µM in A549 cells. The compound was able to reduce colony formation and inhibit cell migration. Morphological changes and cytometry analysis show that the compound induces apoptosis and necrosis in A549 cells. Conclusions These results show that O-propargyllawsone show a cytotoxic effect and may induce apoptosis in A549 cells.

Introdução/Objetivo: Nos últimos anos, houve um aumento significativo na incidência de infecções causadas por fungos, principalmente em pacientes imunossuprimidos. Dentre esses microrganismos, o gênero Candida é o mais frequentemente identificado. Diante do limitado arsenal terapêutico disponível e a crescente taxa de resistência aos antifúngicos torna evidente a necessidade de pesquisar e desenvolver novos agentes antifúngicos. É descrito na literatura o uso de compostos derivados da naftoquinona como agentes antineoplásicos, antiparasitários e antivirais, entretanto o potencial antifúngico ainda é pouco explorado. Nesse contexto, o presente estudo objetivou elucidar o potencial antifúngico in vitro de compostos naftoquinônicos contra Candida albicans. Metodologia: O efeito biológico dos compostos foi avaliado contra Candida spp. por meio da Concentração Inibitória Mínima e Concentração Fungicida Mínima. Para os compostos que apresentaram atividade, foi também determinado o efeito sinérgico através do ensaio de tabuleiro de damas, efeito ressensibilizante com antifúngicos comerciais, cinética de morte, mecanismo de ação, resistência induzida e efeito sobre fatores de virulência (biofilme e transição levedura-hifa) Resultados: Observou-se então que os compostos RGI-20 e APO-4 apresentaram CIM = 16 μg/mL para Candida albicans 10231 sendo fungicidas nessa concentração. Esses mesmos compostos foram capazes de re-sensibilizar os antifúngicos cetoconazol e miconazol, tendo o APO-4 atuado de maneira sinérgica com antifúngicos azólicos (cetoconazol, miconazol, itraconazol) e polienos (nistatina e anfotericina B). RGI-20 e APO-4 apresentaram ainda atividade fungicida máxima em 12 e 6 horas respectivamente, e não apresentaram resistência induzida no período de 21 dias. O efeito antifúngico desses compostos não está relacionado com a capacidade de se ligar ao ergosterol da membrana de leveduras de C. albicans, nem com ação na parede celular através do sorbitol. Em adição, reduziram visualmente a transição levedura-hifa em concentrações subinibitórias, reduziram de maneira significativa a formação de biofilme em concentrações ≥4 μg/mL e também atuaram sobre o biofilme maturo em concentrações ≥128 μg/mL). Conclusão: Em conclusão, os resultados mostram que esses compostos apresentam potente efeito antifúngico in vitro, apresentando atividade promissora no tratamento de infecções superficiais ou invasivas por C. albicans.

Abstract 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).

The title compound, C13H8O3, crystallizes in two polymorphs, namely the monoclinic (space group P21/c) and triclinic (space group Pī) forms, obtained from N,N-dimethylformamide and isopropyl alcohol solutions, respectively. The molecular structures and conformations in the two forms are essentially the same as each other. The naphthoquinone ring systems are essentially planar with r.m.s. deviations of 0.015 and 0.029 Å for the monoclinic and triclinic forms, respectively. The O-propargyl groups are coplanar with the naphthoquinone units with r.m.s deviations ranging from 0.04 to 0.09 Å. In the monoclinic crystal, molecules are linked via pairs of C—H...O hydrogen bonds, forming a tape structure running along [120]. The tapes are further linked by a C—H...π interaction into a layer parallel to the ab plane. Adjacent layers are linked by another C—H...π interaction. In the triclinic crystal, molecules are linked via C—H...O and π–π interactions, forming a layer parallel to the ab plane. Adjacent layers are linked by a C—H...π interaction.

The naphtho-quinone unit of the title compound, C 13 H 8 O 3 , is essentially planar, with an r.m.s. deviation of 0.013 Å for the non-H atoms. The essentially linear propargyl group is tilted by ca 113° relative to the naphtho-quinone plane. In the crystal, mol-ecules are linked via a pair of O-H⋯O hydrogen bonds, forming an inversion dimer. The dimers are further linked via pairs of C-H⋯O hydrogen bonds into a tape structure along [20]. No π-π stacking is observed in the present case as it could be expected for naphtho-quinone derivatives.