In vitro Evaluation of Phthalimide Derivatives Against Cancer Cell lines

Los cánceres de pulmón, próstata e hígado se encuentran entre los más prevalentes en los hombres. El cáncer de mama, de cuello uterino y de tiroides se encuentran entre los más prevalentes en mujeres (OMS, 2019). El tratamiento del cáncer generalmente incluye quimioterapia y radioterapia; sin embargo, los medicamentos contra el cáncer disponibles tienen una selectividad baja y causan efectos adversos graves, como nefrotoxicidad, neurotoxicidad y mielosupresión (Matsuo et al., 2010). Por tanto, el diseño y desarrollo de compuestos como nuevos agentes anticancerígenos frente a los tipos de cáncer de mayor incidencia son de vital importancia en el campo de la salud. Los derivados de ftalimida son compuestos prometedores para el desarrollo de nuevos agentes anticancerígenos (Li et al., 2011; Grigalius y Petrikaite, 2017; Kamal et al., 2002). Basado en lo anterior, Este trabajo tuvo como objetivo evaluar la actividad antiproliferativa de 43 derivados de ftalimida contra una línea celular de cáncer principal en hombres (HepG2) y dos líneas celulares de cáncer principales en mujeres (HeLa y 4T1). Además, se determinó la citotoxicidad de los compuestos contra una línea celular de fibroblasto murino normal (3T3). Los resultados mostraron que los compuestos C16, E11 y E16 presentaron la mejor actividad antiproliferativa contra las líneas celulares HeLa y 4T1. El compuesto H16 solo disminuyó la proliferación celular en un 32% contra la línea celular HepG2. Los compuestos H5, H16, E2, E16 y C1 no afectaron a la proliferación de la línea celular 3T3. Demostrando que sería importante continuar con el análisis de este tipo de compuestos frente a diferentes cánceres para encontrar nuevos compuestos con mejor actividad que los actualmente disponibles en el mercado

Pharmacology Evaluation of Bioactive Compounds that Regulate Cervical Cancer Cells

Cancer has been a public health problem that has gained a lot of death. However, in spite of the advances in the diagnosis and treatment of cervical cancer, women follow the struggle versus this disease. Also, those patients suffer from limited efficacy and specificity, undesirable effects, drug resistance, and a high cost of treatments. Currently, several studies have demonstrated the efficiency of natural products, called bioactive compounds, against cervical cancer cell lines. Bioactive compounds, including polyphenols and phenolic acids or flavonoids, etc., have antioxidant and pro-oxidant properties. These compounds are efficacy and show high specificity because probably they act as anti-oxidant and pro-oxidant. The pro-oxidant activity obstructs growth factors related to different signalling pathways that trigger cancer. Although, usually this kind of compounds helps for dispatching the apoptosis in cervical cancer cell. The aim of this chapter is reviewing how bioactive compounds affect the signalling pathways

Anaerobic Biodegradation of Polyaromatic Hydrocarbons by a Sulfate Reducing Bacteria C1Fd Strain

Aromatic hydrocarbons contamination is widely prevalent in various parts of the world due to anthropogenic activities and leads to anaerobic conditions. As a result, most of its biodegradation is due to anaerobic microorganisms, and most specifically by anaerobic bacteria capable of using sulfates as final electron acceptor to degrade these compounds. Although there are reports on consortia of microorganisms that are involved in the anaerobic biodegradation of monoaromatic hydrocarbons (MAH) and polyaromatic hydrocarbons (PAH), only few reports are available using pure cultures. This paper describes an anaerobic, gram positive and spore forming bacterial strain (C1Fd), which was isolated and purified from aromatic compounds degrading consortium developed using bovine rumen fluid as inoculum. C1Fd was able to use MAH and PAH under anaerobic conditions and removed up 9.4 mM of MAH and 9.2 mM of PAH in less than 72 h. The strain was identified as Bacillus sp. and is phylogenetically related to the hydrocarbon degrading bacteria, Desulfotomaculum sp., isolated from a wastewater treatment plant

Phytochemical and Biological Characterization of the Fractions of the Aqueous and Ethanolic Extracts of <i>Parthenium hysterophorus</i>

In this study, the fractions of the aqueous (AE) and ethanolic (EE) crude extracts of Parthenium hysterophorus were evaluated for their phytochemical composition, cytotoxic, and antioxidant activity. The two extracts were subjected to a fractionation by vacuum liquid chromatography, obtaining seven fractions for each extract. These fractions were evaluated for the presence of phenolic compounds by reverse phase high performance liquid chromatography coupled to mass spectrometer (RP-HPLC-MS) analysis. Their cytotoxic activity was tested with a hemolysis assay. The antioxidant activity was evaluated with the Trolox equivalent antioxidant capacity (TEAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl radical (–OH) scavenging assays. In addition, the effect of the fractions on the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), from human erythrocytes, was evaluated. The phytochemical screening by RP-HPLC-MS mainly showed the presence of flavonoids and hydroxycinnamic acids. The hemolysis assay exhibited a low cytotoxic activity by the fractions of the AE, but the fractions of the EE exhibited a hemolytic effect. The fractions of the AE and EE showed significant antioxidant activity to inhibit radicals in the three radical scavenging assays. Moreover, only some fractions of the AE showed a significant increase in the activity of the SOD enzyme, while the activity of CAT exhibited a significant increase by the fractions of the two extracts. The fractions of the AE and EE of P. hysterophorus have phytochemicals with antioxidant activity to inhibit radicals and increase the activity of in vitro antioxidant enzymes

Comparison of venom composition and biological activities of the subspecies Crotalus lepidus lepidus, Crotalus lepidus klauberi and Crotalus lepidus morulus from Mexico

The rock rattlesnakes Crotalus lepidus comprise a group (lepidus, klauberi, morulus and maculosus) of poorly known mountain cold-tolerant snakes in Mexico. In particular, Crotalus lepidus morulus is a snake endemic of the northeast of Mexico, whereas Crotalus lepidus klauberi and C. l. lepidus are distributed in some regions of the north and central Mexico and southern U. S. Until now very little data are available from C. lepidus subspecies from Mexico, as the terrain inhabited by these snakes is generally steep and rugged. In this work, we have determined some biochemical and biological properties of C. l. morulus, C. l. klauberi and C. l. lepidus crude venoms. Some minor differences in venoms were noted in SDS-PAGE, HPLC profile and MALDI-TOF mass spectrometry analysis. Partial sequences of metalloproteinases, phospholipases A2 (PLA2) and galactose-specific lectins were identified in the venoms. Venoms of C. l. klauberi and C. l. lepidus had significantly higher hemorrhagic and lethal activities than C. l. morulus venom. Proteolytic activity in azocasein was higher in C. l. morulus venom, whereas gelatin hydrolysis was higher in C. l. klauberi. Fibrinogenolytic and PLA2 activities were very similar in all venoms tested. The histological observations in the gastrocnemius muscle damaged by venoms from all the subspecies confirmed myonecrotic and hemorrhagic activities (at 3 and 24 h), which resulted in a poor regenerative response after 14 days. However, C. l. lepidus and C. l. klauberi venom induced a higher increase in the plasma activity of creatine kinase (CK), evidencing higher myotoxicity, whereas paw edema-inducing activity was higher in C. l. lepidus venom. The results indicate that the venoms from the three subspecies have similar protein profiles in electrophoresis, HPLC and molecular weight determinations. However, differences were found in the biological activities in mice. Notably, the venoms of C. l. lepidus and C. l. klauberi present higher toxicity (lower LD50) and hemorrhagic activity than C. l. morulus venom.Mexican National Council for Science and Technology/[SEP-CONACYT-2008-82 833]/CONACYT/MéxicoUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Evaluación biológica in vitro e in silico de derivados de ftalamida como agentes antiproliferativos

Phthalimide is considered a scaffold for the development of new anticancer agents. In this work, the antiproliferative activity of forty-three phthalimide derivatives was evaluated against cervical (HeLa), liver (HepG2), breast (4T1) cancer cell lines, and a normal cell line of murine fibroblasts (3T3). Finally, a molecular docking analysis of phthalimide derivatives on the active site of the enzymes DNA methyltransferase 1 (DNMT1) and vascular endothelial growth factor receptor 2 (VEGR2) as potential drug targets was performed. The compounds, C16, E11, and E16 showed the best antiproliferative activity against the cell lines HeLa and 4T1. Only, the compound H16 decreased 32% cell proliferation against HepG2 cell line. The compounds H5, H16, E2, E16, and C1 did not affect the proliferation of the 3T3 cell line. The molecular docking analysis showed that phthalimide derivatives have a greater affinity for DNMT1 than S-adenosyl-l-homocysteine, a potent DNMT1 inhibitor. However, molecular docking results do not correlate with their antiproliferative effects, suggesting another potential mechanism of action for the active compounds.La estructura de la ftalimida es considerada un bloque de construcción para el desarrollo de nuevos agentes anticancerígenos. En este trabajo, se evaluó la actividad antiproliferativa de cuarenta y tres derivados de ftalimida contra las líneas celulares cancerígenas de cérvix (HeLa), hígado (HepG2), mama (4T1), y la línea celular normal de fibroblastos murinos (3T3). Por último, se realizó un análisis de acoplamiento molecular de los derivados de la ftalimida en el sitio activo de la enzima metiltransferasa 1 de DNA (DNMT1, por sus siglas en inglés) y el receptor del factor de crecimiento endotelial vascular 2 (VEGR2, por sus siglas en inglés) como posibles blancos farmacológicos. Los compuestos C16, E11 y E16 mostraron la mejor actividad antiproliferativa contra las líneas celulares HeLa y 4T1. Solamente, el compuesto H16 disminuyó 32% la proliferación celular de la línea HepG2. Los compuestos H5, H16, E2, E16 y C1 no afectaron la proliferación celular de la línea 3T3. El análisis de acoplamiento molecular demostró que los derivados de la ftalimida tienen una mayor afinidad que la S-adenosil-l-homocisteína, un potente inhibidor de la metiltransferasa 1 de DNA. Sin embargo, los resultados del acoplamiento molecular no se correlacionan con los efectos antiproliferativos; lo cual sugiere que los compuestos activos tienen otro mecanismo de acción

Recovery of Bioactive Ellagitannins by Ultrasound/Microwave-Assisted Extraction from Mexican Rambutan Peel (Nephelium lappaceum L.)

Rambutan (Nephelium lappaceum L.) is a tropical fruit from Asia which has become the main target of many studies involving polyphenolic analysis. Mexico produces over 8 million tons per year of rambutan, generating a huge amount of agro-industrial waste since only the pulp is used and the peel, which comprises around 45% of the fruit&rsquo;s weight, is left behind. This waste can later be used in the recovery of polyphenolic fractions. In this work, emerging technologies such as microwave, ultrasound, and the hybridization of both were tested in the extraction of phenolic compounds from Mexican rambutan peel. The results show that the hybrid technology extraction yielded the highest polyphenolic content (176.38 mg GAE/g of dry rambutan peel). The HPLC/MS/ESI analysis revealed three majoritarian compounds: geraniin, corilagin, and ellagic acid. These compounds explain the excellent results for the biological assays, namely antioxidant activity evaluated by the DPPH, ABTS, and LOI (Lipid oxidation inhibition) assays that exhibited great antioxidant capacity with IC50 values of 0.098, 0.335, and 0.034 mg/mL respectively, as well as prebiotic activity demonstrated by a &micro;Max (maximum growth) of 0.203 for Lactobacillus paracasei. Lastly, these compounds have shown no hemolytic activity, opening the door for the elaboration of different products in the food, cosmetic, and pharmaceutical industries