(E)-N-Benzyl­idene-4H-1,2,4-triazol-4-amine

The title compound, C9H8N4, crystallizes with three independent mol­ecules (A, B and C) per asymmetric unit. The independent mol­ecules differ slightly in their conformations, the dihedral angles between the triazole and phenyl rings in mol­ecules A, B and C being 4.8 (2), 9.7 (2) and 7.2 (2)°, respectively. In the crystal, the independent mol­ecules are linked into a trimer by C—H⋯N hydrogen bonds

N-[(4-Amino-5-sulfanyl­idene-4,5-dihydro-1H-1,2,4-triazol-3-yl)meth­yl]-4-methyl­benzamide

In the title compound, C11H13N5OS, the dihedral angle between the triazole ring and the benzene ring is 84.21 (7)°. The amino group adopts a pyramidal configuration. An intra­molecular N—H⋯O hydrogen bond stabilizes the mol­ecular structure and generates an S(8) ring. In the crystal, mol­ecules are linked by inter­molecular N—H⋯O, N—H⋯S, N—H⋯N and C—H⋯S hydrogen bonds into layers lying parallel to the bc plane. The crystal structure is further stabilized by aromatic π–π stacking inter­actions [centroid–centroid distance = 3.3330 (7) Å]

Actividad antibiofilm de un extracto antibacteriano de schinus fasciculatus y sus componentes

Las bacterias fitopatógenas poseen la capacidad de adherirse y colonizar los tejidos vegetales mediante biofilms. La formación de estas películas bacterianas puede verse afectadas por la presencia de bactericidas en concentraciones sub-letales, algo que sucede comúnmente cuando la aplicación de estos compuestos no es homogénea sobre la superficie de la planta. En este contexto, la actividad antibiofilm de un compuesto antibacteriano podría contribuir al control de enfermedades vegetales que producen grandes pérdidas en los cultivos. En este trabajo se evaluó la capacidad de inhibición de biofilm de un extracto con actividad antimicrobiana de Schinus fasciculatus y sus componentes en concentraciones sub-letales. El extracto foliar fAcet de Schinus fasciculatus y sus componentes, los flavonoides agatisflavona, quercetina, kaempferol se ensayaron en Concentraciones sub-letales previamente establecidas (125-1,9 μg/mL) para determinar su capacidad de inhibir la formación de biofilm de 5 cepas fitopatógenas, Pseudomonas syringae pv tomato Pseudomonas corrugata, Xanthomonas campestris pv vesicatoria, Erwinia carotovora var carotovora y Agrobacterium tumefaciens, mediante el ensayo de cristal violeta en microplaca descripto por O?Toole. Los resultados fueron analizados estadísticamente utilizando los test de Shapiro-Wilk, ANOVA y Kruskal-Wallis del software STATISTICA, version 7. La inhibición de biofilm fue dependiente de la cepa bacteriana, y en menor medida del compuesto ensayado, siendo E. carotovora var. carotovora y A. tumefaciens las más susceptibles, con inhibiciones de entre un 40-80%, mientras que P. corrugata y X. campestres pv vesicatoria fueron las menos susceptibles con una inhibición máxima de un 39%. El extracto y los flavonoides inhibieron en un 40 a 80% la formación de biofilm de las especies bacterianas ensayadas, por lo que en concentraciones sub-letales estos compuestos serían capaces de atenuar la patogenicidad de las bacterias fitopatógenas investigadas.Fil: Terán Baptista, Zareath Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Aredes Fernández, Pedro Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Mandova, T.. Universidad Paris Descartes; FranciaFil: Kritsanida, M.. Universidad Paris Descartes; FranciaFil: Grougnet, R.. Universidad Paris Descartes; FranciaFil: Sampietro, Diego Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaIV Reunión Conjunta de Sociedades de Biología de la República Argentina: nuevas evidencias y cambios de paradigmas en Ciencias BiológicasMendozaArgentinaSociedad de Biología de CórdobaSociedad de Biología de CuyoAsociación de Biología de Tucumá

Phytochemical Investigation and Anticonvulsant Activity of Paeonia parnassica Radix

Based on traditional reports of the use of plants of the genus Paeonia in the treatment of epilepsy, we have screened extracts of the roots of three Greek Paeonia species (P. parnassica, P. mascula subsp. hellenica, P. clusii subsp. clusii) for anticonvulsant activity. This led to the identification of some interesting prophylactic anticonvulsant activity of the extracts of P. parnassica. From the roots of this species, seventeen compounds were subsequently isolated and identified. Amongst these, seven contained the characteristic cage-like terpenic skeleton that is found only in plants of the genus Paeonia. Two of the above products: 4-O-methylpaeoniflorin (1) and paeonidanin (2) are described for the first time as natural products. The structures of all compounds have been elucidated on the basis of their spectral data. © 2007 SAGE Publications Inc

Synthesis and antiproliferative activity of 7-azaindirubin-3′-oxime, a 7-aza isostere of the natural indirubin pharmacophore

The bis-indole alkaloid indirubin and its analogues bear a very interesting natural pharmacophore. They are recognized mainly as kinase inhibitors, but several other activities make them possible candidates for preclinical studies. Based on the previously reported activity of 7-bromoindirubin-3́-oxime and its derivatives, the synthesis of indirubins bearing a heterocyclic nitrogen atom at position 7 was carried out. Herein, we report the first synthesis of 7-azaindirubin-3́-oxime (12) as well as its antiproliferative activity against 57 cancer cell lines and its inhibitory activity against a series of kinases. 7-Azaindirubin (10) and its 3́-oxime derivative (12) showed reduced activity as kinase inhibitors in comparison with other known indirubin derivatives, but antiproliferative activity with a best GI50 value of 0.77 μM. © 2009 American Chemical Society and American Society of Pharmacognosy

Comparative metabolomic study between African and Amazonian Symphonia globulifera by tandem LC–HRMS

According to the literature, the phytochemistry of Symphonia globulifera (Clusiacea) seems to be highly correlated to the local ecosystem. None of the already isolated 31 metabolites from Africa were common with the 13 isolated in French Guiana. Considering the potent therapeutic activities of these metabolites, we have investigated these differences thought a LC–HRMSn conducted metabolomic approach. By using a database correlation and fragmentation patterns, 37 compounds responsible of the variation have been putatively annotated. Among these metabolites, only 6 were already described in this species. This study highlights the relatively restrict phytochemical knowledge of Symphonia globulifera, a species with potent therapeutic metabolites and thus, allow faster phytochemical mapping for further isolation. © 2017 Phytochemical Society of Europ

Symphonia globulifera, a widespread source of complex metabolites with potent biological activities

Symphonia globulifera has been widely used in traditional medicine and has therefore been subjected to several phytochemical studies in the American and African continents. Interestingly, some disparities have been observed concerning its metabolic profile. Several phytochemical studies of S. globulifera have led to the identification of more than 40 compounds, including several polycyclic polyprenylated acylphloroglucinols. Biological evaluations have pointed out the promising biological activities of these secondary metabolites, mostly as antiparasitic or antimicrobial, confirming the traditional use of this plant. The purpose of this review is to describe the natural occurrence, botanical aspects, ethnomedicinal use, structure, and biogenesis, as well as biological activities of compounds isolated from this species according to their provenance. © Georg Thieme Verlag KG Stuttgart.New York

Synthesis and antiviral activity evaluation of some new 6-substituted 3-(1-adamantyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles

A number of novel 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4] thiadiazole derivatives, containing the adamantyl moiety, were synthesized and examined in various viral test systems. No antiviral effects were noted with any of the compounds at subtoxic concentrations in cell culture. © 2002 Published by Éditions scientifiques et médicales Elsevier SAS

3′-substituted 7-halogenoindirubins, a new class of cell death inducing agents

Indirubins are kinase inhibitory bis-indoles that can be generated from various plant, mollusk, mammalian, and bacterial sources or chemically synthesized. We here report on the synthesis and biological evaluation of 3′-substituted 7-halogenoindirubins. Molecular modeling and kinase assays suggest that steric hindrance prevents 3′-substituted 7-halogenoindirubins from interacting with classical kinase targets of other indirubins such as cyclin-dependent kinases and glycogen synthase kinase-3. Surprisingly 3′-substituted 7-halogeno-indirubins induce cell death in a diversity of human tumor cell lines. Although some 3′-substituted 7-halogenoindirubins appear to induce effector caspase-independent, nonapoptotic cell death, others trigger the landmarks of classical apoptosis. A structure-activity relationship study was performed to optimize 3′-substituted 7-halogenoindirubins with respect to solubility and cell death induction. Despite their unidentified targets, 3′-substituted 7-halogenoindirubins constitute a new promising family of antitumor agents. © 2006 American Chemical Society

A novel 7-bromoindirubin with potent anticancer activity suppresses survival of human melanoma cells associated with inhibition of STAT3 and Akt signaling

STAT3 and Akt signaling have been validated as potential molecular targets for treatment of cancers including melanoma. These small molecule inhibitors of STAT3 or Akt signaling are promising for developing anti-melanoma therapeutic agents. MLS-2438, a novel 7-bromoindirubin, a derivative of the natural product indirubin, was synthesized with a bromo-group at the 7-position on one indole ring and a hydrophilic group at the 3'-position on the other indole ring. We tested the anticancer activity of MLS-2438 and investigated its mechanism of action in human melanoma cell lines. Here, we show that MLS-2438 inhibits viability and induces apoptosis of human melanoma cells associated with inhibition of STAT3 and Akt signaling. Several pro-apoptotic Bcl-2 family proteins are involved in the MLS-2438 mediated apoptosis. MLS-2438 inhibits Src kinase activity in vitro and phosphorylation of JAK2, Src, STAT3 and Akt in cultured cancer cells. In contrast to the decreased phosphorylation levels of JAK2, Src, STAT3 and Akt, phosphorylation levels of the MAP K (Erk1/2) signaling protein were not reduced in cells treated with MLS-2438. These results demonstrate that MLS-2438, a novel natural product derivative, is a Src inhibitor and potentially regulates kinase activity of JAK2 and Akt in cancer cells. Importantly, MLS-2438 suppressed tumor growth with low toxicity in a mouse xenograft model of human melanoma. Our findings support further development of MLS-2438 as a potential small-molecule therapeutic agent that targets both STAT3 and Akt signaling in human melanoma cells. © 2012 Landes Bioscience