Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction.

A series of 1,5-disubstituted tetrazole-indole hybrids were synthesized via a high-order multicomponent reaction consisting of an Ugi-azide/Pd/Cu-catalyzed hetero-annulation cascade sequence. This operationally simple one-pot protocol allowed high bond-forming efficiency and creating six new bonds (two C-C, three C-N, and one N-N). Additionally, the products were evaluated against breast cancer MCF-7 cells, finding moderate activity in the compounds substituted with fluorine and chlorine.

Gold(I)-Catalyzed Synthesis of 2,2'-Biindoles via One-Pot Double Cycloisomerization Strategy.

The first systematic, concise and target-directed gold(I)-catalyzed synthesis of a family of 2,2'-biindoles containing different substitution patterns is described. The developed protocol involves the synthesis of 1,3-diyne-anilines followed by a one-pot gold(I)-catalyzed double cycloisomerization, giving rise to an efficient, broad and general protocol to get different 2,2'-biindoles under mild reaction conditions. Due to the methodological restriction of present methods for accessing this class of compounds, herein we present our synthetic proposal which allowed the preparation of several examples of 2,2'-biindoles.

A one-pot five component reaction for the synthesis of tetrazol-benzofuran hybrids and their inhibitory activity against .

A synthetic strategy for obtaining a new series of 1,5-disubstituted tetrazole-benzofuran hybrid systems a one-pot five-component reaction is described. This process involves a Ugi-azide multicomponent reaction coupled to an intramolecular cyclization catalyzed by Pd/Cu, resulting in low to moderate yields from 21 to 67%. This protocol allowed the synthesis of highly substituted benzofurans at the 2-position through an operationally simple process under mild reaction conditions and with high bond forming efficiency due to the formation of six new bonds (two C-C, two C-N, one N-N, and one C-O).

A Metastable Semiquinone Molecular Switch Modulated by Ascorbate/O: A Study from a System Far-From-Equilibrium to Biological Assays in Mitochondria.

A molecular switch based on the metastable radical anion derived from a substituted heteroaryl quinone is described. Pyrrolyl quinone thiocyanate (PQ 9) showed an interaction with the fluoride anion that was visible to the naked eye and quantified by UV/vis and 1H and 13 C NMR. The metastable quinoid species formed by the interaction with F ("ON" state) showed a molecular switching effect autocontrolled by the presence of ascorbate ("OFF" state) and back to the "ON" state by an autooxidation process, measured by visible and UV/vis spectroscopy.

Differential Effect of 4-Benzo[] [1, 3]oxazines on the Proliferation of Breast Cancer Cell Lines.

Background: A family of 4-benzo[][1,3]oxazines were obtained from a group of -(2-alkynyl)aryl benzamides precursors via gold(I) catalysed chemoselective 6--dig C-O cyclization.

Method: The precursors and oxazines obtained were studied in breast cancer cell lines MCF-7, CAMA-1, HCC1954 and SKBR-3 with differential biological activity showing various degrees of inhibition with a notable effect for those that had an aryl substituted at C-2 of the molecules. 4-benzo[][1,3]oxazines showed an IC rating from 0.

Proliferation, Migration and Invasion of Breast Cancer Cell Lines Are Inhibited by 1,5-Disubstituted Tetrazol-1,2,3-triazole Hybrids through Interaction with p53.

The anticarcinogenic potential of a series of 1,5-disubstituted tetrazole-1,2,3-triazole hybrids (T-THs) was evaluated in the breast cancer (BC)-derived cell lines MCF-7 (ER+, PR+, and HER2-), CAMA-1 (ER+, PR+/-, and HER2-), SKBR-3 (ER+, PR+, and HER2+), and HCC1954 (ER+, PR+, and HER2+). The T-THs , , and inhibited the proliferation of MCF-7 and CAMA-1, HCC1954, and SKBR-3 cells, respectively. The compounds with stronger effect in terms of migration and invasion inhibition were , , , and for the CAMA-1, MCF-7, HCC1954, and SKBR-3 cells respectively.

Derivates of 1,6-dihyadroazaazulenes as inhibitors of tyrosine kinases BCR-ABL1 wild type and mutant T315I: a molecular dynamics approach.

The protein tyrosine kinase (PTK) produced by the BCR-ABL1 gene has generated significant interest in the development of inhibitors since the presence of punctual mutations causes resistance to currently approved drugs, mainly the mutation has been the most difficult to address. In this work, derivatives of 1,6-dihydroazaazulenes are studied as possible inhibitors of this PTK in its wild form and the mutant . The recognition of the ligands was explored through molecular docking, and the stability of the complexes and their evolution over time was studied using molecular dynamics (MD) simulations.

Gold(I)-Catalyzed Synthesis of 4-Benzo[][1,3]oxazines and Biological Evaluation of Activity in Breast Cancer Cells.

The first gold(I)-catalyzed cycloisomerization procedure applied to the synthesis of substituted 4-benzo[][1,3]oxazines has been developed starting from -(2-alkynyl)aryl benzamides. The chemoselective oxygen cyclization via the 6--dig pathway yielded the observed heterocycles in modest to good chemical yields under very mild reaction conditions. The obtained oxazines were assayed on the breast cancer (BC)-derived cell lines MCF-7 and HCC1954 with differential biological activity.

Novel 2-aryl-4-aryloxyquinoline-based fungistatics for Mucor circinelloides. Biological evaluation of activity, QSAR and docking study.

Zygomycetes are ubiquitous saprophytes in natural environments which transform organic matter. Some zygomycetes of gender Mucor have attracted interest in health sector. Due to its ability as opportunistic microorganisms infecting immuno-compromised people and to the few available pharmacological treatments, the mucormycosis is receiving worldwide attention.

Prediction of the impact induced by Cd in binary interactions with other divalent metals on wild-type and Cd-resistant strains of Dictyosphaerium chlorelloides.

The metals present in freshwater have a toxic profile with bioaccumulation and are biomagnified along the aquatic food chain. The metals induce high sensitivity in most aquatic organisms, while others, such as some microalgae species, evolve towards resistance. Therefore, this research predicted through the Combination Index method the binary interaction exposed to divalent metals by inhibiting population growth in a Cd-resistant strain (Dc) compared to the wild-type strain (Dc1M) of Dictyosphaerium chlorelloides and evaluate the specific resistance level obtained by Dc to Cd relative to other divalent metals.

()-3-Hydroxy-3-(4-R-Phenyl)-Prop-2-Enedithioic Acids as New Antituberculosis Compounds.

Background: Tuberculosis is an infectious disease caused by the bacillus . Compounds including a sulfur-containing scaffold have been shown to be key scaffolds in various antituberculosis agents. Interestingly, the 3-hydroxy-3-phenyl-prop-2-enedithioic acids have, to the best of our knowledge, not been previously described as antituberculosis agents.

A One-Pot Six-Component Reaction for the Synthesis of 1,5-Disubstituted Tetrazol-1,2,3-Triazole Hybrids and Their Cytotoxic Activity against the MCF-7 Cell Line.

A high-order multicomponent reaction involving a six-component reaction to obtain the novel linked 1,5-disubstituted tetrazole-1,2,3-triazole hybrids in low to moderate yield is described. This one-pot reaction is carried out under a cascade process consisting of three sequential reactions: Ugi-azide, bimolecular nucleophilic substitution (S2), and copper-catalyzed alkyne-azide reaction (CuAAC), with high atom and step-economy due the formation of six new bonds (one C-C, four C-N, and one N-N). Thus, the protocol developed offers operational simplicity, mild reaction conditions, and structural diversity.

Cooperative Recognition of Ni Triggered by Fluoride Ions in Naturally Occurring α-Hydroxyquinone Derivatives.

Perezone is a naturally occurring hydroxyquinone that has been deeply studied from different chemical aspects, such as therapeutics, electrochemistry, physical-chemical properties, or synthetic approaches that turn it an attractive template for new semisynthetic derivatives with a wide range of purposes. Herein, we describe a facile synthetic pathway to obtain new perezone derivatives by the addition of a pyrrole moiety that can be used for ion recognition. Compounds showed the capability to interact with several anions and M cations as separate events that result in colorimetric changes.

Molecular docking and pharmacophoric modelling of 1,5-disubstituted tetrazoles as inhibitors of two proteins present in cancer, the ABL and the mutated T315I kinase.

A docking study of a set of several 1,5-disubstituted tetrazoles compounds has been performed to predict the poses of some potential inhibitors of the Abelson tyrosine-protein kinase and the mutated Abelson tyrosine-protein kinase T315I. The study was conducted through Lamarckian genetic algorithms in Autodock4 package. Bayesian calculations were performed; specificity and sensitivity values as well as positive predicted values, and negative predicted values were calculated using a set of 99 known experimentally active ligands and 385 decoys for the Abelson tyrosine-protein kinase from the Directory of Useful Decoys database.

Deep Eutectic Solvent Choline Chloride/-toluenesulfonic Acid and Water Favor the Enthalpy-Driven Binding of Arylamines to Maleimide in Aza-Michael Addition.

Deep eutectic solvents (DESs) have been considered "the organic reaction medium of the century" because they can be used as solvents and active catalysts in chemical reactions. However, experimental and theoretical studies are still needed to provide information on the structures of DESs, the kinetics and thermodynamics properties, the interactions between the DESs and the substrates, the effect of water on the DES supramolecular network and its physicochemical properties, and so forth. This information is very useful to understand the essence of the processes that take place in the catalysis of chemical reactions and, therefore, to help in the design of a DES for a specific reaction and sample.

Evolution in the photosynthetic oxygen rate of a Cd-resistant strain of Dictyosphaerium chlorelloides by changes in light intensity and temperature.

Environmental factors such as temperature and light are the most determinants in the photosynthetic productivity in microalgae. However, under extreme of these conditions, certain resistant microalgae strains possess additional abilities such as growth in the presence of high concentrations of metals and some can improve in combinations of more than one abiotic stress. Therefore, the aim of this research was to evaluate the efficiency in photosynthetic production through the oxygen balance to variations in photon intensity, and under temperature changes in a Cd-resistant strain (Dc) compared to the wild-type strain (Dc1M) of Dictyosphaerium chlorelloides.

Oxidative amidation of benzaldehyde using a quinone/DMSO system as the oxidizing agent.

An efficient transition-metal-based heterogeneous catalyst free procedure for obtaining the oxidative amidation of benzaldehyde using quinones as oxidizing agents in low molar proportions is described here. Pyrrolylquinones (PQ) proved to be more suitable than DDQ and 2,5-dimethylbenzoquinone to conduct the oxidation process. Although the solvent itself acted as the oxidant with low to moderate yields, PQ/DMSO provided an efficient system for carrying out the reaction under operational simplicity, mild reaction conditions, short reaction times and high yields of the desired product.

A novel 4-aminoantipyrine-Pd(II) complex catalyzes Suzuki-Miyaura cross-coupling reactions of aryl halides.

A simple and efficient catalytic system based on a Pd complex of 4-aminoantipyrine, 4-AAP-Pd(II), was found to be highly active for Suzuki-Miyaura cross-coupling of aryl iodides and bromides with phenylboronic acids under mild reaction conditions. Good to excellent product yields from the cross-coupling reaction can be achieved when the reaction is carried out in ethanol, in the open air, using low loading of 4-AAP-Pd(II) as a precatalyst, and in the presence of aqueous K2CO3 as the base. A variety of functional groups are tolerated.

A Novel Semisynthetic Anion Receptor: Synthesis and Ion Recognition of (1-H-pyrrol-2-yl)-4-oxo-perezone.

We describe the synthesis of the novel 2-(1,5-dimethyl-4-oxo-hexyl)-3-hydroxy-5-methyl-6-pyrrolyl-1,4-benzoquinone 2 from the natural product perezone 1. The anion-guest properties of the new compound were evaluated in the presence of fluoride, chloride, bromide and iodide tetrabutylammonium salts using 1H NMR titration techniques in deuterated dichloromethane or dimethylformamide. The title compound showed interesting colorimetric behavior in the presence of inorganic salts.

The first direct synthesis of beta-unsubstituted meso-decamethylcalix[5]pyrrole.

The first direct synthesis of beta-unsubstituted meso-decamethylcalix[5]pyrrole from pyrrole and acetone, with moderate yield, is described. The results showed that a bismuth salt was necessary to obtain calix[5]pyrrole, with the best results obtained using Bi(NO(3))(3).

Synthesis and in vitro cytotoxic activity of pyrrolo[2,3-e]indole derivatives and a dihydro benzoindole analogue.

The synthesis of pyrrolo[2,3-e]indole derivatives with the structural characteristics of DNA bis- and mono-intercalators are described. A dihydro benzoindol analogue was also synthesised to elucidate the major structural requirements for cytotoxic activity. A biological evaluation of the test compounds was carried out in six different tumoral cell lines.