(-)-Oleacein and (-)-oleocanthal, two phenolic compounds present in Extra Virgin Olive Oil, inhibit angiogenesis

Phenolic compounds in the Mediterranean diet contribute to many of the health-related benefits accounted in this dietary choice. (-)-Oleocanthal and the less studied (-)-oleacein, are two phenolic compounds present in the Extra Virgin Olive Oil that have shown anti-tumoural effects both in vitro and in vivo. Among their effects on cancer, they could inhibit tumour cell migration and invasion, key processes also in angiogenesis, the process by which de novo blood vessels are formed. Herein, we explored the anti-angiogenic potential of (-)-oleocanthal and (-)-oleacein in a comparative study in in vitro experiments on endothelial cells, and in two in vivo models. (-)-Oleocanthal and (-)-oleacein affected endothelial viability in the micromolar range, as well as the formation of tubule-like structures by these cells, and their migration. Interestingly, only oleacein inhibited cell migration and induced apoptosis significantly. Regarding cellular signalling, both compounds were able to reduce the activation of the AKT and ERK1/2 pathways, which are related to survival and proliferation, respectively. Finally, both compounds showed anti-angiogenic activity in a zebrafish model of regeneration and in the chicken chorioallantoic membrane. Altogether, these results support the anti-angiogenic potential of (-)-oleocanthal and (-)-oleacein, and suggest that (-)-oleacein exerts more potent effects on endothelial cell migration and induction of apoptosis. Thus, we propose these two phenolic compounds, with a special focus on (-)-oleacein, as new candidates for clinical use as anti-cancer and anti-angiogenic agents. [Grants: PID2019-105010RB-I00 and RTI2018-098560-BC22 (Spanish Government), UMA18-FEDERJA-220, and PY20_00257 (Andalusian Government and FEDER). Funds from BIO 267 (Andalusian Government). CIBERER, CIBERCV].Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

(−)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic Modulation

The antioxidant and anti-inflammatory responses of (−)-methyl-oleocanthal (met-OLE), a new metabolite of the extra virgin olive oil (EVOO) phenolic oleocanthal (OLE), were explored in lipopolysaccharide (LPS)-induced murine peritoneal macrophages. Possible signaling pathways and epigenetic modulation of histones were studied. Met-OLE inhibited LPS-induced intracellular reactive oxygen species (ROS) and nitrite (NO) production and decreased the overexpression of the pro-inflammatory enzymes COX-2, mPGES-1 and iNOS in murine macrophages. In addition, met-OLE was able to significantly decrease the activation of p38, JNK, and ERK mitogen-activated protein kinases (MAPKs) and blocked canonical and non-canonical inflammasome signaling pathways. On the contrary, met-OLE upregulated haem oxigenase 1 (HO-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) expression in treated cells. Finally, met-OLE pretreated spleen cells counteracted LPS induction, preventing H3K18 acetylation or H3K9 and H3K27 demethylation. Overall, these results provide novel mechanistic insights into the beneficial effects of met-OLE regarding the regulation of the immune–inflammatory response through epigenetic changes in histone markers. This revealing evidence suggests that the methylated metabolite of OLE may contribute significantly to the beneficial effects that are associated with the secoiridoid-related compound and the usual consumption of EVOO.España Ministerio de Economía y Competitividad grant number AG-2017-89342-PJunta de Andalucía funded by CTS-259, FQM-18

Effect of Extraction Conditions on the Antioxidant Activity of Olive Wood Extracts

An investigation to optimize the extraction yield and the radical scavenging activity from the agricultural by-product olive tree wood (Olea europaea L., cultivar Picual) using six different extraction protocols was carried out. Four olive wood samples from different geographical origin, and harvesting time have been used for comparison purposes. Among the fifty olive wood extracts obtained in this study, the most active ones were those prepared with ethyl acetate, either through direct extraction or by successive liquid-liquid partitioning procedures, the main components being the secoiridoids oleuropein and ligustroside. An acid hydrolysis pretreatment of olive wood samples before extractions did not improve the results. In the course of this study, two compounds were isolated from the ethanolic extracts of olive wood collected during the olives' harvesting season and identified as (7 R)-7 -ethoxyoleuropein (1) and (7 S)-7 -ethoxyoleuropein (2)

The Extra Virgin Olive Oil phenolic compounds () oleacein and () oleocanthal inhibit tumor cell autophagy

Es una comunicación a congreso internacional en formato póster.Our group has recently shown that the antitumor Extra Virgin Olive Oil phenolic compounds (—)oleocanthal and (—)oleacein also behave as antiangiogenic agents. Interestingly, it has been described that phenolic compounds found in the Mediterranean diet affect the autophagy pathway. Based on this background, we studied the modulatory effects of (—)oleocanthal and (—)oleacein on tumor cell autophagy. Methodologically, the tumor cell lines MDAMB231, MCF7 and HT1080 cell lines were used in in vitro cellular and molecular studies of the autophagy flux and key mediators of this process, and High Content Screening (HCS) System using Perkin Elmer Operetta for single-cell analysis was performed in these cells. Interestingly, (—)oleocanthal and (—)oleacein repressed the autophagy flux of MDAMB231 and MCF7 submitted to autophagy inducing conditions (severe starving) at doses in the low micromolar range. In addition, key autophagy mediators, like LC3 or WIPI2 proteins, were dramatically reduced in the same settings, as seen in immunohistochemical studies. Furthermore, preliminary results of HCS in tumor cells revealed depletory effects on autophagy by using specifics dyes for this process at the single-cell level. Altogether, our results point to a drastic inhibitory effect of (—)oleocanthal and (—)oleacein on tumor cell autophagy at low doses.[Grants: PID2022-138181OB-I00, PID2019-105010RB-I00 and RTI2018-098560-BC22 (Spanish Government), UMA18-FEDERJA-220, and PY20_00257 (Andalusian Government and FEDER). Funds from BIO 267 (Andalusian Government) M.B. is supported by “Juan de la Cierva – Incorporation Program” (IJC2018-037657-I), Spanish Ministry of Science and Innovation, Spain.]. Supported with a a help from the «II Plan Propio de Investigación, Transferencia y Divulgación Científica de la UMA», Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Programa de Tutorías Personalizadas en la Licenciatura de Química

Son muchas las novedades a las que se enfrenta el estudiante a su llegada a la Universidad. Acostumbrados a un grupo reducido de amigos y profesores del instituto local, la Universidad les abre la posibilidad inquietante de salir por primera vez de casa, de conocer nuevos compañeros y amigos, de conocer nuevas formas de enseñanza y estudio, de relacionarse con gente de diversas nacionalidades y profesión.Por todo esto, conscientes por nuestra experiencia con alumnos de cursos anteriores de que todas estas novedades no serán fáciles de asimilar y avalados por los informes de evaluación de la Titulación de Química de la UJA (interno y externo), que detectan importantes deficiencias en el proceso de enseñanza-aprendizaje, un grupo de profesores de la Universidad hemos considerado interesante y especialmente formativo ofrecer a los alumnos nuestra ayuda en la forma de un servicio de tutorización personalizado, mediante el cual y desde una perspectiva más cercana se puedan mejorar todos estos aspectos

Synthesis and <i>h</i>LDH Inhibitory Activity of Analogues to Natural Products with 2,8-Dioxabicyclo[3.3.1]nonane Scaffold

Human lactate dehydrogenase (hLDH) is a tetrameric enzyme present in almost all tissues. Among its five different isoforms, hLDHA and hLDHB are the predominant ones. In the last few years, hLDHA has emerged as a therapeutic target for the treatment of several kinds of disorders, including cancer and primary hyperoxaluria. hLDHA inhibition has been clinically validated as a safe therapeutic method and clinical trials using biotechnological approaches are currently being evaluated. Despite the well-known advantages of pharmacological treatments based on small-molecule drugs, few compounds are currently in preclinical stage. We have recently reported the detection of some 2,8-dioxabicyclo[3.3.1]nonane core derivatives as new hLDHA inhibitors. Here, we extended our work synthesizing a large number of derivatives (42–70) by reaction between flavylium salts (27–35) and several nucleophiles (36–41). Nine 2,8-dioxabicyclo[3.3.1]nonane derivatives showed IC50 values lower than 10 µM against hLDHA and better activity than our previously reported compound 2. In order to know the selectivity of the synthesized compounds against hLDHA, their hLDHB inhibitory activities were also measured. In particular, compounds 58, 62a, 65b, and 68a have shown the lowest IC50 values against hLDHA (3.6–12.0 µM) and the highest selectivity rate (>25). Structure–activity relationships have been deduced. Kinetic studies using a Lineweaver–Burk double-reciprocal plot have indicated that both enantiomers of 68a and 68b behave as noncompetitive inhibitors on hLDHA enzyme

Ácidos resínicos de la madera de juniperus sabina L. y juniperus oxycedrus L.

La fracción ácida del extracto de hexano de la madera de Juniperus sabina L., está constituída mayoritariamente por ácido trans-comúnico y además contiene ácido cis-comúnico, isocuprésico y sandaracopimárico. La fracción ácida del extracto hexánico de la madera de Juniperus oxycedrus L., presenta como componentes mayoritarios trans-comúnico e isocuprésico y también están presentes ácido agático, 15-0-metilisocuprésico, 13-oxo-14,15-dinor-labd-8(17)-en-19-oico, abiético, dehidroabiético, palústrico, neoabiético y sandaracopimárico.Acidic fraction of hexane extract from wood of Junipérus sabina L. mainly contains trans-communic acid. Furthemore cis-communic, isocupres sic and sandaracopimaric acids have been isolated and identified. Equivalent fraction from wood of Juniperus sabina L. mainly contains isocupressic and trans-communic acids. Furthemore agatic, 15-0-methylisocupressic, 13-oxo14,15-dinor-labd-8(l7)-en-19-oic, abietic, dehydroabietic, palustric, neoabie tic and sandaracopimaric acids, are present into this extract

Procedimiento para la preparación de productos olorosos tipo ámbar gris a partir de ácidos comúnicos

Número de publicación: ES 2 069 469. Número de solicitud: 9300946Procedimiento para la preparación de productos olorosos tipo ámbar gris a partir de ácidos comúnicos. Se presenta un procedimiento de síntesis del fijador(-)-8α,12-epoxi-13,14,15,16-tetranorlabdano, registrado con el nombre de Ambrox® por Firmenich S.A., a partir de una muestra de origen natural constituida por una mezcla de E/Z de comunatos de metilo.Durante el procedimiento seguido se sintetizan y caracterizan los siguientes productos intermedios: -12-hidroxi-13,14,15,16-tetranorlabd-8(17)-en19-oa to de metilo, -8α,12-epoxi-13,14,15,16-tetranorlabdan-19-oato de metilo, -8α,12-epoxi-13,14,15,16-tetranorlabdan-19-ol, -8α,12-epoxi-13,14,15,16-tetranorlabdan-19-al.Universidad de Granad

Procedimientos de obtención de ámbrox a partir de diterpenos labdánicos naturales

Número de solicitud: 9200779. Número de publicación: ES 2 044 780Procedimientos de obtención de ámbrox a partir de diterpenos labdánicos naturales. La presente intervención consiste en sendos procedimientos de síntesis de (-)-8a,12-epoxi-13,14,15.16-tetranorlabdano, más conocido como (-)-Ambrox (nombre registrado por Firmenich, S.A.), a partir de esclareol y cisabienol. Durante los procedimientos planteados se sintetizan tambi én los siguientes productos intermedios: 8a-acetoxi-13,14,15,16-tetranorlabdan-12- al, ácido 8a-acetoxi-13,14,15,16-tetranorlabdan-12- oico, 13,14,15,16-tetranorlabdano-8a,12-diol.Universidad de Granad