Selective activity of 2,4-diaryl-1,2,3,4-tetrahydroquinolines on Trypanosoma cruzi epimastigotes and amastigotes expressing β-galactosidase

Fonseca-Berzal, Cristina; Arenas, Diego; Bohórquez, Arnold R. Romero; Escario, José Antonio; Kouznetsov, Vladímir V.; Gómez‐Barrio, Alicia

doi:10.1016/j.bmcl.2013.06.079

Cited by 36 publications

(24 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…40 Formulations with a low cytotoxicity for mammalian cells (< 20% inhibition) 41 were tested for their activity against epimastigotes chosen for preliminary screening because of its simple maintenance and relatively high drug sensitivity. 42 Drug activity was evaluated using the colorimetric method 43,44 . Absorbances and cell counts were compared to determine their correlation under the conditions of our laboratory.…”

Section: Methodsmentioning

confidence: 99%

Benznidazole Nanoformulates: A Chance to Improve Therapeutics for Chagas Disease

Vinuesa

Herráez

Oliver

et al. 2017

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

This article describes the characterization of various encapsulated formulations of benznidazole, the current first-line drug for the treatment of Chagas disease. Given the adverse effects of benznidazole, safer formulations of this drug have a great interest. In fact, treatment of Chagas disease with benznidazole has to be discontinued in as much as 20% of cases due to side effects. Furthermore, modification of delivery and formulations could have potential effects on the emergence of drug resistance. The trypanocidal activity of new nanostructured formulations of benznidazole to eliminate Trypanosoma cruzi was studied in vitro as well as their toxicity in two cultured mammalian cell lines (HepG2 and Fibroblasts). Nanoparticles tested included nanostructured lipid carriers, solid lipid nanoparticles, liposomes, quatsomes, and cyclodextrins. The in vitro cytotoxicity of cyclodextrins–benznidazole complexes was significantly lower than that of free benznidazole, whereas their trypanocidal activity was not hampered. These results suggest that nanostructured particles may offer improved therapeutics for Chagas disease.

show abstract

Section: Methodsmentioning

confidence: 99%

Benznidazole Nanoformulates: A Chance to Improve Therapeutics for Chagas Disease

Vinuesa

Herráez

Oliver

et al. 2017

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

show abstract

“…2 y 3) se logró la identificación y el desarrollo de nuevos agentes antiparasitarios. Entre varias moléculas líderes se destacan la 6-etil-2-fenilquinolina (6-Et-Qu) que fue capaz de inhibir el crecimiento de promastigotes de Leishmania braziliensis y reducir el número de amastigotes intracelulares, bloqueando la biosíntesis del esterol del protozoo vía la acumulación del esqualeno y la disminución del nível de 5-hidroepisterol (Bompart et al, 2013); las 3-metil-tetrahidroquinolinas (1-B-THQ, 6-CN-THQ) que mostraron efecto inhibidor del crecimiento de Trypanosoma cruzi en epimastigotes y amastigotes, y citotoxicidad inespecífica sobre fibroblastos NCTC-929, alcanzando altos índices de selectividad en la forma extracelular y una gran selectividad en la etapa intracelular (Fonseca-Berzal et al, 2013) (Fig. 4).…”

Section: Figura1unclassified

“…38(Supl. ): [129][130][131][132][133][134][135][136][137][138][139][140][141]2014 valores de TEAC igual o mayor que la de antioxidantes conocidos, tal como α-tocoferol Merchán et al, 2013).…”

Section: Figura1unclassified

Conexión de Biología y Química vía Síntesis Orgánica dirigida a la Diversidad molecular

Kouznetsov

2014

Rev. Acad. Colomb. Cienc. Ex. Fis. Nat.

Self Cite

View full text Add to dashboard Cite

"La unión interdisciplinaria de los mundos de la química y la biología debe comenzarse con la comprensión de los campos de desempeño de las dos disciplinas".Stuart Schreiber ResumenEl enorme progreso en el entendimiento de los sistemas biológicos y del funcionamiento de los fármacos dentro del cuerpo humano se debe a la unión de la química y la biología y a la aplicación inteligente de los principios y técnicas de la química orgánica. Ésta juega el papel de iniciador en el descubrimiento biológico impulsando el diseño y desarrollo de nuevos fármacos. Utilizando tácticas sintéticas modernas de la química orgánica, la síntesis dirigida a la diversidad permite preparar diversas moléculas (fármacos, agentes biológicos) que son valiosos modelos para el estudio de las complejas interacciones biológicas de los organismos vivos. Los resultados y logros del LQOBio se discuten en esta revisión prestando atención al desarrollo de algunos aspectos de la síntesis verde y la biología química que ha venido haciendo el LQOBio estos últimos años.Palabras claves: síntesis dirigida a la diversidad, moléculas pequeñas, heterociclos, bioensayos in vitro e in vivo. Connection between Biology and Chemistry via Diversity Oriented Synthesis AbstractThe enormous progress in the understanding of biological systems and the functioning of the drugs within the human body is due to the union of chemistry and biology and the intelligent application of the principles and techniques of organic chemistry. This plays the role of initiator in biological discovery driving the design and development of new drugs. Using tactics of modern synthetic organic chemistry, diversity-directed synthesis allows preparation of various molecules (drugs, biological agents) that are valuable models for the study of complex biological interactions of living organisms. The results and achievements of the LQOBio are discussed in this review with attention to the development of some aspects of green synthesis and chemical biology that has been doing the LQOBio recent years. IntroducciónLa química orgánica, la biología y la física son las columnas primarias que sostienen el templo de la ciencia que estudia y trata de entender los procesos fundamentales de la vida de los seres vivos. El enorme progreso en el entendimiento de los sistemas biológicos y del funcionamiento de los fármacos dentro del cuerpo humano se debe a la aplicación inteligente de los principios y técnicas de la química orgánica.La química orgánica juega el papel del iniciador en el descubrimiento biológico, en el diseño y desarrollo de nuevos fármacos. Desde hace muchos años la biología "se movió "desde del nivel descriptivo y fenomenológico hasta el nivel molecular y bioquímico. En consecuencia, nuevas disciplinas como la biología estructural, la biología molecular y la genética molecular fueron creadas y desarrolladas (Waldmann y Janning, 2004).Los seres vivos producen y liberan al medio diversos compuestos químicos (productos naturales) que afectan de manera significativa a otros organismos y partic...

show abstract

“…Quinones generate reactive oxygen species (ROS), which not only results in their antitumor properties, but also in a mechanism for designing antichagasic drugs. Here, a synthetic series of seven chromenoazoldiones previously defined as potential antitumorals [2,3], has been assayed in vitro against Trypanosoma cruzi (CL-B5 lacZ strain) in a primary screening that evaluates activity over epimastigotes and toxicity on L929 cells [4,5]. Compounds PM199, PM203 and PM401 achieved higher IC50 values than that of the reference drug benznidazole (BZ): IC50 = 14.45 ± 1.90, 14.84 ± 4.49, 16.01 ± 9.06 and 36.47 ± 4.43 µM (PM199, PM203, PM401 and BZ, respectively).…”

mentioning

confidence: 99%

In Vitro Primary Screening of a Synthetic Series of Chromenoazoldiones against Trypanosoma cruzi

Fonseca-Berzal

Morales

Escario

et al. 2017

Proceedings of the 1st Molecules Medicinal Chemistry Symposium, Barcelona, Spain

Self Cite

View full text Add to dashboard Cite

Similarities between parasites and cancer have prompted parasitologists to take advantage of several approaches enabled by cancer research to identify antiparasitic agents [1]. Quinones generate reactive oxygen species (ROS), which not only results in their antitumor properties, but also in a mechanism for designing antichagasic drugs. Here, a synthetic series of seven chromenoazoldiones previously defined as potential antitumorals [2,3], has been assayed in vitro against Trypanosoma cruzi (CL-B5 lacZ strain) in a primary screening that evaluates activity over epimastigotes and toxicity on L929 cells [4,5]. Compounds PM199, PM203 and PM401 achieved higher IC50 values than that of the reference drug benznidazole (BZ): IC50 = 14.45 ± 1.90, 14.84 ± 4.49, 16.01 ± 9.06 and 36.47 ± 4.43 µM (PM199, PM203, PM401 and BZ, respectively). However, their higher cytotoxicity led to a lower selectivity (SI) on epimastigotes: SIPM199 = 5.83, SIPM203 = 7.03, SIPM401 = 5.27 and SIBZ > 7.02. Only two compounds showed no cytotoxicity (LC50 > 256 µM) and thus, no derivative was further assayed against intracellular amastigotes. These chromenoazoldiones did not show relevant activity on T. cruzi. Their cytotoxicity, probably connected to ROS production in mammalian cells, encourages further optimization to apply them as trypanocidal templates.

show abstract

Selective activity of 2,4-diaryl-1,2,3,4-tetrahydroquinolines on Trypanosoma cruzi epimastigotes and amastigotes expressing β-galactosidase

Cited by 36 publications

References 46 publications

Benznidazole Nanoformulates: A Chance to Improve Therapeutics for Chagas Disease

Benznidazole Nanoformulates: A Chance to Improve Therapeutics for Chagas Disease

Conexión de Biología y Química vía Síntesis Orgánica dirigida a la Diversidad molecular

In Vitro Primary Screening of a Synthetic Series of Chromenoazoldiones against Trypanosoma cruzi

Contact Info

Product

Resources

About