A Straightforward Method for Synthesizing Bioactive Resorcinolic Lipid Analogues

Resorcinolic lipids, a class of bioactive amphiphilic molecules found widely in nature, hold potential for a variety of biological and industrial applications. This report describes the synthesis of three bioactive structural analogues of resorcinolic lipids, obtained by subjecting ethyl (E)-2-undecenoate and ethyl acetoacetate to a Michael reaction in the presence of sodium ethoxide to generate a Michael adduct, followed by cyclization in the reaction medium. Ethyl 2-octyl-4,6-dioxocyclohexanecarboxylate (7) was thus produced with a 60% yield. To perform an aromatization step, 7 was subsequently treated with I2 in methanol under reflux, producing a combined 80% yield of 2,4-dimethoxy-6-octyl-ethyl benzoate (1) and 2-hydroxy-4-methoxy-6-octyl-ethyl benzoate (2) at a 7:3 ratio, respectively. 2-Hydroxy-4-methoxy-6-octyl-benzoic acid was obtained with a 60% yield by treating 1 with BBr3/CHCl3. The structures of the synthesized compounds and intermediates were elucidated by 1H and 13C NMR spectroscopy, employing two-dimensional techniques (HSQC and HMBC). DOI: http://dx.doi.org/10.17807/orbital.v12i2.23

A Straightforward Method for Synthesizing Bioactive Resorcinolic Lipid Analogues

Resorcinolic lipids, a class of bioactive amphiphilic molecules found widely in nature, hold potential for a variety of biological and industrial applications. This report describes the synthesis of three bioactive structural analogues of resorcinolic lipids, obtained by subjecting ethyl (E)-2-undecenoate and ethyl acetoacetate to a Michael reaction in the presence of sodium ethoxide to generate a Michael adduct, followed by cyclization in the reaction medium. Ethyl 2-octyl-4,6-dioxocyclohexanecarboxylate (7) was thus produced with a 60% yield. To perform an aromatization step, 7 was subsequently treated with I2 in methanol under reflux, producing a combined 80% yield of 2,4-dimethoxy-6-octyl-ethyl benzoate (1) and 2-hydroxy-4-methoxy-6-octyl-ethyl benzoate (2) at a 7:3 ratio, respectively. 2-Hydroxy-4-methoxy-6-octyl-benzoic acid was obtained with a 60% yield by treating 1 with BBr3/CHCl3. The structures of the synthesized compounds and intermediates were elucidated by 1H and 13C NMR spectroscopy, employing two-dimensional techniques (HSQC and HMBC). DOI: http://dx.doi.org/10.17807/orbital.v12i2.23

Análisis de la eficiencia de un biofiltro a base de levadura Saccharomyces Cerevisiae y piedras pómez para la remoción de DBO5 en agua residuales domésticas en el AA.HH. Primavera en Carabayllo, 2019

El trabajo de investigación se enfocó en desarrollar una alternativa para la reducción de los contaminantes biológicos de Agua Residual Doméstica para poder permitir una mejor calidad del agua, para lo cual se elaboró un sistema de Biofiltración en el cual se utilizaron Hongos del tipo levadura de la especie Saccharomyces cerevisiae, adheridas a un soporte de piedra pómez, formándose una biopelícula que absorbía el oxígeno disuelto presente en el agua residual doméstica. Se usó dicha agua residual de un hogar común, para ver los efectos y a fin de evaluar la eficiencia del sistema de un Biofiltro, se inició con el acondicionamiento y la adaptación del hongo con una solución azucarada, se midieron directamente los parámetros de Oxígeno Disuelto (OD), Potencial de Hidrógeno (pH), sólidos totales (ST) y Demanda Biológica De Oxígeno (DBO5) en un periodo de 7 días. En la eficiencia del Biofiltro los resultados que se obtuvieron permitieron tener valores de remoción promedio DBO5= 14.7%, pH= 13.4%, ST=23.31% y OD = 10,84% El sistema de biofiltración estudiado, demostró que tiene eficiencias altas para el plazo de 7 días en remoción de materia orgánica

Telomeric Heterochromatin Propagation and Histone Acetylation Control Mutually Exclusive Expression of Antigenic Variation Genes in Malaria Parasites

SummaryMalaria parasites use antigenic variation to avoid immune clearance and increase the duration of infection in the human host. Variation at the surface of P. falciparum-infected erythrocytes is mediated by the differential control of a family of surface antigens encoded by var genes. Switching of var gene expression occurs in situ, mostly from telomere-associated loci, without detectable DNA alterations, suggesting that it is controlled by chromatin structure. We have identified chromatin modifications at telomeres that spread far into telomere-proximal regions, including var gene loci (>50 kb). One type of modification is mediated by a protein homologous to yeast Sir2 called PfSir2, which forms a chromosomal gradient of heterochromatin structure and histone hypoacetylation. Upon activation of a specific telomere-associated var gene, PfSir2 is removed from the promoter region and acetylation of histone occurs. Our data demonstrate that mutually exclusive transcription of var genes is linked to the dynamic remodeling of chromatin

Caminhos Sintéticos para Novos Lipídeos Resorcinólicos Análogos às Citosporonas.

Neste trabalho, foi planejada a síntese de lipídeos resorcinólicos análogos as citosporonas utilizando métodos clássicos de síntese orgânica. O objetivo principal foi à preparação dos compostos: ácido 2,4-dihidróxi-6-octil-benzóico (6) e 2,4-diidróxi-6-(8-oxooctil)-benzóico (7). Foram estudadas rotas de síntese visando à produção desses compostos, foi possível obtenção de três intermediários avançados, com sucesso: 2,4 dimetóxi-6-octil-benzoato de etila (8), 2-hidróxi-4-metóxi-6-octil-benzoato de etila (9) e ácido 2-hidróxi-4-metóxi-6-octil-benzóico (10), os quais tiveram suas estruturas determinadas por técnicas de espectroscopia de RMN de 1H e de 13C, e no caso de (10) incluindo técnicas bidimensionais (HSQC e HMBC).</p

Artigo Original: A toxicological evaluation of hepatocytes exposed to the synthetic resorcinolic lipid 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one. PECIBES, 18-23, 2017.

Recent studies showed that resorcinolic lipid 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one (AMS 35AA) may be an important chemotherapy adjuvant, that is not genotoxic nor mutagenic. It is noteworthy that, when AMS35AA is associated with cyclophosphamide, it increases the mutagenic damage, splenic phagocytosis, neutropenia, and induces apoptosis in liver and kidneys. Taken this into account, the present study performed an accurate morphometric investigation of the consequences of the association between AMS35AA and cyclophosphamide on the hepatocytes morphology of Swiss mice. Our results provide strong evidence that the AMS35AA is not toxic and does not induce cellular hyperplasia or hypertrophy in the hepatocytes, which could lead the development of malignant neoplasia. Then, our data support the view that the resorcinolic lipid derivative is not toxic to the hepatocyte, which therefore could have therapeutic applications

In vivo chemotherapeutic insight of a novel isocoumarin (3-hexyl-5,7-dimethoxy-isochromen-1-one): Genotoxicity, cell death induction, leukometry and phagocytic evaluation

Abstract Chemotherapy is one of the major approaches for the treatment of cancer. Therefore, the development of new chemotherapy drugs is an important aspect of medicinal chemistry. Chemotherapeutic agents include isocoumarins, which are privileged structures with potential antitumoral activity. Herein, a new 3-substituted isocoumarin was synthesized from 2-iodo-3,5-dimethoxy-benzoic acid and oct-1-yne in a cross-coupling Sonogashira reaction followed by a copper iodide-catalyzed intramolecular cyclization as key step using MeOH/Et3N as the solvent system. The present study also evaluated the leukometry, phagocytic activity, genotoxic potential and cell death induction of three different doses (5 mg/kg, 10 mg/kg and 20 mg/kg) of this newly synthesized isocoumarin, alone and in combination with the commercial chemotherapeutic agents cyclophosphamide (100 mg/kg) and cisplatin (6 mg/kg) in male Swiss mice. The results suggest that the isocoumarin has genotoxicity and causes cell death. Noteworthy, this new compound can increase splenic phagocytosis and lymphocyte frequency, which are related to immunomodulatory activity. When combined with either cyclophosphamide or cisplatin, chemopreventive activity led to a reduction in the effects of both chemotherapeutic drugs. Thus, the new isocoumarin is not a candidate for chemotherapeutic adjuvant in treatments using cyclophosphamide or cisplatin. Nevertheless, the compound itself is an important prototype for the development of new antitumor drugs