RESUMEN
Invited for the cover of this issue are the groups of Holger Braunschweig at the Julius-Maximilians-Universität Würzburg, Germany and Eufrânio N. da Silva Júnior at the Universidade Federal de Minas Gerais, UFMG, Brazil. The image depicts the electrochemical synthesis of selenium-containing BODIPY molecules with lightning symbolizing the electrifying synthetic process, while the surrounding elemental chaos hints at the red-shifted absorption and emission and the transformative photophysical properties of these new compounds. Read the full text of the article at 10.1002/chem.202303883.
RESUMEN
We report a rapid, efficient, and scope-extensive approach for the late-stage electrochemical diselenation of BODIPYs. Photophysical analyses reveal red-shifted absorption - corroborated by TD-DFT and DLPNO-STEOM-CCSD computations - and color-tunable emission with large Stokes shifts in the selenium-containing derivatives compared to their precursors. In addition, due to the presence of the heavy Se atoms, competitive ISC generates triplet states which sensitize 1 O2 and display phosphorescence in PMMA films at RT and in a frozen glass matrix at 77â K. Importantly, the selenium-containing BODIPYs demonstrate the ability to selectively stain lipid droplets, exhibiting distinct fluorescence in both green and red channels. This work highlights the potential of electrochemistry as an efficient method for synthesizing unique emission-tunable fluorophores with broad-ranging applications in bioimaging and related fields.
Asunto(s)
Selenio , Estructura Molecular , Compuestos de Boro , Fluorescencia , Colorantes FluorescentesRESUMEN
Transition-metal catalyzed C-H activation reactions have been proven to be useful methodologies for the assembly of synthetically meaningful molecules. This approach bears intrinsic peculiarities that are important to be studied and comprehended in order to achieve its best performance. One example is the use of additives for the in situ generation of catalytically active species. This strategy varies according to the type of additive and the nature of the pre-catalyst that is being used. Thus, silver(I)-salts have proven to play an important role, due to the resulting high reactivity derived from the pre-catalysts of the main transition metals used so far. While being powerful and versatile, the use of silver-based additives can raise concerns, since superstoichiometric amounts of silver(I)-salts are typically required. Therefore, it is crucial to first understand the role of silver(I) salts as additives, in order to wisely overcome this barrier and shift towards silver-free systems.
RESUMEN
In recent decades, the incidence of candidemia in tertiary hospitals worldwide has substantially increased. These infections are a major cause of morbidity and mortality; in addition, they prolong hospital stays and raise the costs associated with treatment. Studies have reported a significant increase in infections by non-albicans Candida species, especially C. tropicalis. The number of antifungal drugs on the market is small in comparison to the number of antibacterial agents available. The limited number of treatment options, coupled with the increasing frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. The objective of this study was to evaluate and compare the antifungal activities of three semisynthetic naphthofuranquinone molecules against fluconazole-resistant Candida spp. strains. These results allowed to us to evaluate the antifungal effects of three naphthofuranquinones on fluconazole-resistant C. tropicalis. The toxicity of these compounds was manifested as increased intracellular ROS, which resulted in membrane damage and changes in cell size/granularity, mitochondrial membrane depolarization, and DNA damage (including oxidation and strand breakage). In conclusion, the tested naphthofuranquinones (compounds 1-3) exhibited in vitro cytotoxicity against fluconazole-resistant Candida spp. strains.
Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Farmacorresistencia Fúngica/efectos de los fármacos , Fluconazol/farmacología , Naftoquinonas/farmacología , Animales , Antifúngicos/síntesis química , Antifúngicos/química , Candida/clasificación , Candida/genética , Candida tropicalis/efectos de los fármacos , Candida tropicalis/genética , Candida tropicalis/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Daño del ADN , ADN de Hongos/química , ADN de Hongos/genética , ADN de Hongos/metabolismo , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Modelos Químicos , Datos de Secuencia Molecular , Estructura Molecular , Naftoquinonas/síntesis química , Naftoquinonas/química , Fosfatidilserinas , ARN Ribosómico 5.8S/genética , Especies Reactivas de Oxígeno/metabolismo , Análisis de Secuencia de ADNRESUMEN
1,2,3-Triazole-, arylamino- and thio-substituted naphthoquinones (24, 8, and 2 representatives, respectively) were synthesized in moderate yields and evaluated against several human cancer cell lines (blood, ovarian, breast, central nervous system, colon, and prostate cancers and melanoma), showing, for some of them, IC50 values below 2 µM. The cytotoxic potential of the tested naphthoquinones was also assayed on non-tumor cells such as human peripheral blood mononucluear cells (PBMC) and two murine fibroblast lines (L929 and V79 cells). α-Lapachone- and nor-α-lapachone-based 1,2,3-triazoles and arylamino-substituted naphthoquinones showed potent cytotoxicity against different cancer cell lines. The compounds may represent promising new lead derivatives for anticancer drug development. The electrochemical properties of selected compounds were evaluated in an attempt to correlate them with antitumor activity.
Asunto(s)
Naftoquinonas/química , Triazoles/química , Proliferación Celular , Química Clic , Humanos , Modelos Moleculares , Estructura Molecular , Relación Estructura-ActividadRESUMEN
In our continued search for novel trypanocidal compounds, twenty-six derivatives of para- and ortho-naphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17-24, 28-30 and 36-38 are described herein for the first time. Three of these novel compounds (28-30) were found to be more potent than the standard drug benznidazole, with IC50/24h values between 6.8 and 80.8µM. Analysis of the toxicity to heart muscle cells led to LC50/24h of <125, 63.1 and 281.6µM for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent.
Asunto(s)
Naftoquinonas/química , Triazoles/química , Tripanocidas/síntesis química , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cristalografía por Rayos X , Técnicas Electroquímicas , Electrodos , Ratones , Conformación Molecular , Miocitos Cardíacos/citología , Relación Estructura-Actividad , Triazoles/síntesis química , Triazoles/toxicidad , Tripanocidas/química , Tripanocidas/toxicidad , Trypanosoma cruzi/efectos de los fármacosRESUMEN
Continuing our screening program for novel anti-parasite compounds, we synthesized seven 1,4-naphthoquinones coupled to 1,2,3-triazoles, five nor-ß-lapachone-based 1,2,3-triazoles and ten α-lapachone-based 1,2,3-triazoles. These and other naphthoquinonoid compounds were evaluated for their activity against promastigote forms of antimony-sensitive and -resistant strains of Leishmania infantum (syn. Leishmania chagasi) and Leishmania amazonensis. The toxicity of these compounds to mammalian cells was also examined. The substances were more potent than an antimonial drug, with IC50 values ranging from 1.0 to 50.7 µM. Nor-α-lapachone derivatives showed the highest antileishmanial activity, with selectivity indices in the range of 10-15. These compounds emerged as important leads for further investigation as antileishmanial agents. Additionally, one of these compounds exhibited cross-resistance in Sb-resistant Leishmania and could provide a molecular tool for investigating the multidrug resistance mechanisms in Leishmania parasites.
Asunto(s)
Antiprotozoarios/síntesis química , Reacción de Cicloadición/métodos , Naftoquinonas/síntesis química , Triazoles/síntesis química , Alquinos/química , Animales , Antimonio/farmacología , Antiprotozoarios/química , Antiprotozoarios/farmacología , Azidas/química , Catálisis , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cobre/química , Resistencia a Medicamentos/efectos de los fármacos , Leishmania/efectos de los fármacos , Leishmania infantum/efectos de los fármacos , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/efectos de los fármacos , Ratones , Naftoquinonas/química , Naftoquinonas/farmacología , Pruebas de Sensibilidad Parasitaria , Especificidad de la Especie , Triazoles/química , Triazoles/farmacologíaRESUMEN
Five 2-hydroxy-3-substituted-aminomethyl naphthoquinones, nine 1,2,3-triazolic para-naphthoquinones, five nor-ß-lapachone-based 1,2,3-triazoles, and several other naphthoquinonoid compounds were synthesized and evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease, continuing our screening program for new trypanocidal compounds. Among all the substances, 16-18, 23, 25-29 and 30-33 were herein described for the first time and fifteen substances were identified as more potent than the standard drug benznidazole, with IC(50)/24h values in the range of 10.9-101.5 µM. Compounds 14 and 19 with Selectivity Index of 18.9 and 6.1 are important structures for further studies.