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Large-pore channels, including those formed by connexin, pannexin, innexin proteins, are part of a broad family of plasma membrane channels found in vertebrates and invertebrates, which share topology features. Despite their relevance in parasitic diseases such as Chagas and malaria, it was unknown whether these large-pore channels are present in unicellular organisms. We identified 14 putative proteins in Trypanosomatidae parasites as presumptive homologs of innexin proteins. All proteins possess the canonical motif of the innexin family, a pentapeptide YYQWV, and 10 of them share a classical membrane topology of large-pore channels. A sequence similarity network analysis confirmed their closeness to innexin proteins. A bioinformatic model showed that a homolog of Trypanosoma cruzi (T. cruzi) could presumptively form a stable octamer channel with a highly positive electrostatic potential in the internal cavities and extracellular entrance due to the notable predominance of residues such as Arg or Lys. In vitro dye uptake assays showed that divalent cations-free solution increases YO-PRO-1 uptake and hyperosmotic stress increases DAPI uptake in epimastigotes of T. cruzi. Those effects were sensitive to probenecid. Furthermore, probenecid reduced the proliferation and transformation of T. cruzi. Moreover, probenecid or carbenoxolone increased the parasite sensitivity to antiparasitic drugs commonly used in therapy against Chagas. Our study suggests the existence of innexin homologs in unicellular organisms, which could be protein subunits of new large-pore channels in unicellular organisms.

Alzheimer's disease (AD) is a degenerative neurological disease characterized by gradual loss of cognitive skills and memory. The exact pathogenesis involved still remains unrevealed, but several studies indicate the involvement of an array of different enzymes, underlining the multifactorial character of the disease. Inhibition of these enzymes is therefore a powerful approach in the development of AD treatments, with promising candidates, including acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase. Interestingly, AChE is the target of a major pesticide family (organophosphates), with several reports indicating an intersection between the pesticide's activity and AD. In this study, various TADDOL derivatives were synthesized and their in vitro activities as AChE/BuChE inhibitors as well as their antioxidant activities were studied. Molecular modeling studies revealed the capability of TADDOL derivatives to bind to AChE and induce inhibition, especially compounds 2b and 3c furnishing IC

The occurrence of intercellular channels formed by pannexin1 has been challenged for more than a decade. Here, we provide an electrophysiological characterization of exogenous human pannexin1 (hPanx1) cell–cell channels expressed in HeLa cells knocked out for connexin45. The observed hPanx1 cell–cell channels show two phenotypes: O-state and S-state. The former displayed low transjunctional voltage (Vj) sensitivity and single-channel conductance of ∼175 pS, with a substate of ∼35 pS; the latter showed a peculiar dynamic asymmetry in Vj dependence and single-channel conductance identical to the substate conductance of the O-state. S-state hPanx1 cell–cell channels were also identified between TC620 cells, a human oligodendroglioma cell line that endogenously expresses hPanx1. In these cells, dye and electrical coupling increased with temperature and were strongly reduced after hPanx1 expression was knocked down by small interfering RNA or inhibited with Panx1 mimetic inhibitory peptide. Moreover, cell–cell coupling was augmented when hPanx1 levels were increased with a doxycycline-inducible expression system. Application of octanol, a connexin gap junction (GJ) channel inhibitor, was not sufficient to block electrical coupling between HeLa KO Cx45-hPanx1 or TC620 cell pairs. In silico studies suggest that several arginine residues inside the channel pore may be neutralized by hydrophobic interactions, allowing the passage of DAPI, consistent with dye coupling observed between TC620 cells. These findings demonstrate that endogenously expressed hPanx1 forms intercellular cell–cell channels and their unique properties resemble those described in innexin-based GJ channels. Since Panx1 is ubiquitously expressed, finding conditions to recognize Panx1 cell–cell channels in different cell types might require special attention.

Background and purpose: The transient receptor potential vanilloid 4 (TRPV4) cation channel participates in multiple physiological processes and is also at the core of different diseases, making this channel an interesting pharmacological target with therapeutic potential. However, little is known about the structural elements governing its inhibition. Experimental approach: We have now combined in silico drug discovery and molecular dynamics simulation based on Xenopus tropicalis xTRPV4 structure with functional studies measuring cell Ca2+ influx mediated by human TRPV4 channel to characterize the binding site of known TRPV4 inhibitors and to identify novel small molecule channel modulators. Key results: We have found that the inhibitor HC067047 binds to a pocket conformed by residues from S2-S3 linker (xTRPV4-D542), S4 (xTRPV4-M583 and Y587 and S5 (xTRPV4-D609 and F613). This pocket was also used for structure-based virtual screening in the search of novel channel modulators. Forty potential hits were selected based on the lower docking scores (from ~250,000 compounds) and their effect upon TRPV4 functionally tested. Three were further analysed for stability using molecular dynamics simulation and functionally tested on TRPV4 channels carrying mutations in the binding pocket. Compound NSC151066, shown to require residue xTRPV4-M583 for its inhibitory effect, presented an IC50 of 145 nM and demonstrated to be an effective antiviral against Zika virus with a potency similar to HC067047. Conclusion and implications: Together, we propose structural insights into the inhibition of TRPV4 and how this information can be used for the design of novel channel modulators. We thank Dr. Andres Merits (University of Tartu, Estonia) for kindly providing the plasmid encoding the ZIKV with NanoLuc, Spanish Ministry of Economy and Competitiveness through grants RTI2018‐099718 (to M.A.V.) and BFU2016‐80039‐R (to J.D.), an institutional “Unidad de Excelencia María de Maeztu” CEX2018‐000792‐M and FEDER funds. F.G.‐N. thanks Fondecyt Regular projects 1170733, the US Army of USA, W911NF‐14‐1‐0520 and The Centro Interdisciplinario de Neurociencia de Valparaíso is a Millennium Institute supported by the Millennium Scientific Initiative of the Ministerio de Economía, Fomento y Turismo P029‐022‐F.

The most common denominator of many of the neurodegenerative diseases is badly folded protein accumulation, which results in the formation of insoluble protein deposits located in different parts of the organism, causing cell death and tissue degeneration. Dendritic systems have turned out to be a promising new therapeutic approach for the treatment of these diseases due to their ability to modulate the folding of these proteins. With this perspective, and focused on type 2 diabetes (T2D), characterized by the presence of deposits containing the amyloidogenic islet amyloid polypeptide (IAPP), we demonstrate how different topologies of cationic carbosilane dendrimers inhibit the formation of insoluble protein deposits in pancreatic islets isolated from transgenic Tg-hIAPP mice. Also, the results obtained by the modification of dendritic carbosilane wedges with the chemical chaperone 4-phenylbutyric acid (4-PBA) at the focal point confirmed their potential as anti-amyloid agents with a concentration efficiency in their therapeutic action five orders of magnitude lower than that observed for free 4-PBA. Computational studies, which determined the main interaction between IAPP and dendrimers at the atomic level, support the experimental work.

In an attempt to rationalize the search for new potential anti-inflammatory compounds on the COX-2 enzyme, we carried out an in silico protocol that successfully combines the prediction of physicochemical and pharmacokinetic properties, molecular docking, molecular dynamic simulation, and free energy calculation. Starting from a small library of compounds synthesized previously, it was found that 70% of the compounds analyzed satisfy with the associated values to physicochemical principles as key evaluation parameters for the drug-likeness; all the compounds presented good gastrointestinal absorption and cerebral permeability and they showed an interaction with the Arg 106 residue of the COX-2 isoenzyme. Finally, it was obtained that compound 3ab has a binding mode, binding energy, and stability in the active site of COX-2 like the reference drug celecoxib, suggesting that this compound could become a powerful candidate in the inhibition of the COX-2 enzyme. In addition, we realized the crystallographic analysis of compounds 3j, 3r, and 3t defining the crystal parameters and the Packing interactions.

The skin and soft tissue infections (SSTIs) -producing pathogens have acquired resistance to a wide range of antimicrobials, thus it is highly relevant to have new treatment alternatives. In this study, we report the synthesis, characterization, and antibacterial activity of three novel series of ionic liquids (ILs) derived from benzoic and hydroxybenzoic acids, with different lengths of the alkyl chain. The minimum inhibitory concentration (MIC) were tested in Gram-positive: Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes, and Gram-negative: Acinetobacter baumannii and Escherichia coli, showing a MIC range of 0.01562-2.0 mM, with the activity varying according to the aromatic ring functionalization and the length of the alkyl chains. Regarding the antibiofilm activity, different efficacy was observed among the different ILs, some of them presenting antibiofilm activities close to 80% as in the case of those derived from syringic acid with an alkyl chain of six carbon atoms against Pseudomonas aeruginosa. Furthermore, the cell viability in HaCaT cells was determined, showing a half maximal effective concentration (EC

NOD1 is an intracellular receptor that, when activated, induces gene expression of pro-inflammatory factors promoting macrophages and neutrophils recruitment at the infection site. However, iE-DAP, the dipeptide agonist that promotes this receptor's activation, cannot permeate cell membranes. To develop a nanocarrier capable of achieving a high and prolonged activation over time, iE-DAP was encapsulated in nanoparticles (NPs) made of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). The physicochemical properties, colloidal stability, encapsulation efficiency, and cellular uptake of iE-DAP-loaded PHVB NPs were analyzed. Results evidenced that physicochemical properties of iE-DAP-loaded NPs remained stable over time, and NPs were efficiently internalized into cells, a process that depends on time and concentration. Moreover, our results showed that NPs elicited a controlled cargo release in vitro, and the encapsulated agonist response was higher than its free form, suggesting the possibility of activating intracellular receptors triggering an immune response through the release of NOD1 agonist.

Motivation Molecular docking is aimed at predicting the conformation of small-molecule (ligands) within an identified binding site (BS) in a target protein (receptor). Protein–ligand docking plays an important role in modern drug discovery and biochemistry for protein engineering. However, efficient docking analysis of proteins requires prior knowledge of the BS, which is not always known. The process which covers BS identification and protein–ligand docking usually requires the combination of different programs, which require several input parameters. This is furtherly aggravated when factoring in computational demands, such as CPU-time. Therefore, these types of simulation experiments can become a complex process for researchers without a background in computer sciences. Results To overcome these problems, we have designed an automatic computational workflow (WF) to process protein–ligand complexes, which runs from the identification of the possible BSs positions to the prediction of the experimental binding modes and affinities of the ligand. This open-access WF runs under the Galaxy platform that integrates public domain software. The results of the proposed method are in close agreement with state-of-the-art docking software. Availability and implementation Software is available at: https://pistacho.ac.uma.es/galaxy-bitlab. Contact euv@uma.es Supplementary information Supplementary data are available at Bioinformatics online.

The imino‐Diels‐Alder reaction is one of the most common strategies in organic chemistry and is an important tool for providing a broad spectrum of biologically active heterocyclic systems. A combined theoretical and experimental study of the imino‐Diels‐Alder reaction is described. The new phenanthroline‐tetrahydroquinolines were evaluated as cholinesterase inhibitors. Their cytotoxicity in human neuroblastoma SH‐SY5Y cells was also evaluated. The theoretical results suggest that compounds formation in stages can be explained by endo cycloadducts under the established reaction conditions, thereby confirming experimental results obtained for percentage yield. These results allowed us to establish that pyridine substituent remarkably influences activation energy and reaction yield, as well as in acetylcholinesterase (AChE) activity. Among these derivatives, compounds with 4‐pyridyl and 4‐nitrophenyl showed favorable AChE activity and proved to be non‐cytotoxic.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, presenting the most devastating consequences on human health and life quality. Coumarin-quinoline hybrids were synthesized following a very efficient and versatile strategy. Small structural variations contributed to dual acetyl/butyrylcholinesterases (AChE/BuChE) activity or selectivity towards one of these enzymes. In addition, some of the studied compounds are interesting iron chelators, presenting a tendency to be neuroprotective. Moreover, the compounds are not cytotoxic for SH-SY5Y neuroblastoma cells. Compound 9c proved to be the most interesting compound of the studied series. This compound is selective against AChE and proved to be an excellent iron chelating agent (iron chelation at 100 μM=72.87%). Molecular docking studies were performed to establish the nature of the interaction between the studied compounds and the binding pockets, leading to a rationalization of structure–activity relationships. Compound 9c forms a well-defined π-stacking interaction with Phe330 and interacts with Tyr121 residue via a hydrogen bond, while the inactive compounds cannot establish these interactions. Important preliminary results against different targets, as well as some structure–activity relationships, were concluded from the experimental results.

The proteins connexins, innexins, and pannexins are the subunits of non-selective channels present in the cell membrane in vertebrates (connexins and pannexins) and invertebrates (innexins). These channels allow the transfer of ions and molecules across the cell membrane or, and in many cases, between the cytoplasm of neighboring cells. These channels participate in various physiological processes, particularly under pathophysiological conditions, such as bacterial, viral, and parasitic infections. Interestingly, some anti-parasitic drugs also block connexin- or pannexin-formed channels. Their effects on host channels permeable to molecules that favor parasitic infection can further explain the anti-parasitic effects of some of these compounds. In this review, the effects of drugs with known anti-parasitic activity that modulate non-selective channels formed by connexins or pannexins are discussed. Previous studies that have reported the presence of these proteins in worms, ectoparasites, and protozoa that cause parasitic infections have also been reviewed.

Several antidepressants inhibit nicotinic acetylcholine receptors (nAChRs) in a non-competitive and voltage-dependent fashion. Here, we asked whether antidepressants with a different structure and pharmacological profile modulate the rat α7 nAChR through a similar mechanism by interacting within the ion-channel. We applied electrophysiological (recording of the ion current elicited by choline, ICh, which activates α7 nAChRs from rat CA1 hippocampal interneurons) and in silico approaches (homology modeling of the rat α7 nAChR, molecular docking, molecular dynamics simulations, and binding free energy calculations). The antidepressants inhibited ICh with the order: norfluoxetine ~ mirtazapine ~ imipramine &lt, bupropion ~ fluoxetine ~ venlafaxine ~ escitalopram. The constructed homology model of the rat α7 nAChR resulted in the extracellular vestibule and the channel pore is highly negatively charged, which facilitates the permeation of cations and the entrance of the protonated form of antidepressants. Molecular docking and molecular dynamics simulations were carried out within the ion−channel of the α7 nAChR, revealing that the antidepressants adopt poses along the receptor channel, with slightly different binding-free energy values. Furthermore, the inhibition of ICh and free energy values for each antidepressant-receptor complex were highly correlated. Thus, the α7 nAChR is negatively modulated by a variety of antidepressants interacting in the ion−channel.

Pannexin 1 channels located in the cell membrane are permeable to ions, metabolites, and signaling molecules. While the activity of these channels is known to be modulated by phosphorylation on T198, T308, and S206, the possible involvement of other putative phosphorylation sites remains unknown. Here, we describe that the activity of Panx1 channels induced by mechanical stretch is reduced by adenosine via a PKA-dependent pathway. The mechanical stretch-induced activity&mdash, measured by changes in DAPI uptake&mdash, of Panx1 channels expressed in HeLa cell transfectants was inhibited by adenosine or cAMP analogs that permeate the cell membrane. Moreover, inhibition of PKA but not PKC, p38 MAPK, Akt, or PKG prevented the effects of cAMP analogs, suggesting the involvement of Panx1 phosphorylation by PKA. Accordingly, alanine substitution of T302 or S328, two putative PKA phosphorylation sites, prevented the inhibitory effect of cAMP analogs. Moreover, phosphomimetic mutation of either T302 or S328 to aspartate prevented the mechanical stretch-induced activation of Panx1 channels. A molecular dynamics simulation revealed that T302 and S328 are located in the water&ndash, lipid interphase near the lateral tunnel of the intracellular region, suggesting that their phosphorylation could promote conformational changes in lateral tunnels. Thus, Panx1 phosphorylation via PKA could be modulated by G protein-coupled receptors associated with the Gs subunit.

Overcoming refractory epilepsy's resistance to the combination of antiepileptic drugs (AED), mitigating side effects, and preventing sudden unexpected death in epilepsy are critical goals for therapy of this disorder. Current therapeutic strategies are based primarily on neurocentric mechanisms, overlooking the participation of astrocytes and microglia in the pathophysiology of epilepsy. This review is focused on a set of non-selective membrane channels (permeable to ions and small molecules), including channels and ionotropic receptors of neurons, astrocytes, and microglia, such as: the hemichannels formed by Cx43 and Panx1; the purinergic P2X7 receptors; the transient receptor potential vanilloid (TRPV1 and TRPV4) channels; calcium homeostasis modulators (CALHMs); transient receptor potential canonical (TRPC) channels; transient receptor potential melastatin (TRPM) channels; voltage-dependent anion channels (VDACs) and volume-regulated anion channels (VRACs), which all have in common being activated by epileptic activity and the capacity to exacerbate seizure intensity. Specifically, we highlight evidence for the activation of these channels/receptors during epilepsy including neuroinflammation and oxidative stress, discuss signaling pathways and feedback mechanisms, and propose the functions of each of them in acute and chronic epilepsy. Studying the role of these non-selective membrane channels in epilepsy and identifying appropriate blockers for one or more of them could provide complementary therapies to better alleviate the disease.

SARS-CoV-2 ORF3a is believed to form ion channels, which may be involved in the modulation of virus release, and has been implicated in various cellular processes like the up-regulation of fibrinogen expression in lung epithelial cells, downregulation of type 1 interferon receptor, caspase-dependent apoptosis, and increasing IFNAR1 ubiquitination. ORF3a assemblies as homotetramers, which are stabilized by residue C133. A recent cryoEM structure of a homodimeric complex of ORF3a has been released. A lower-resolution cryoEM map of the tetramer suggests two dimers form it, arranged side by side. The dimer’s cryoEM structure revealed that each protomer contains three transmembrane helices arranged in a clockwise configuration forming a six helices transmembrane domain. This domain’s potential permeation pathway has six constrictions narrowing to about 1 Å in radius, suggesting the structure solved is in a closed or inactivated state. At the cytosol end, the permeation pathway encounters a large and polar cavity formed by multiple beta strands from both protomers, which opens to the cytosolic milieu. We modeled the tetramer following the arrangement suggested by the low-resolution tetramer cryoEM map. Molecular dynamics simulations of the tetramer embedded in a membrane and solvated with 0.5 M of KCl were performed. Our simulations show the cytosolic cavity is quickly populated by both K+ and Cl-, yet with different dynamics. K+ ions moved relatively free inside the cavity without forming proper coordination sites. In contrast, Cl- ions enter the cavity, and three of them can become stably coordinated near the intracellular entrance of the potential permeation pathway by an inter-subunit network of positively charged amino acids. Consequently, the central cavity’s electrostatic potential changed from being entirely positive at the beginning of the simulation to more electronegative at the end.

Indexación: Scopus. The transient receptor potential vanilloid 1 (TRPV1) ion channel is a member of the family of Transient Receptor Potential (TRP) channels that acts as a molecular detector of noxious signals in primary sensory neurons. Activated by capsaicin, heat, voltage and protons, it is also well known for its desensitization, which led to the medical use of topically applied TRPV1 agonist capsaicin for its long-lasting analgesic effects. Here we report three novel small molecules, which were identified using a Structure-Based Virtual Screening for TRPV1 from the ZINC database. The three compounds were tested using electrophysiological assays, which confirmed their capsaicin-like agonist activity. von Frey filaments were used to measure the analgesic effects of the compounds applied topically on tactile allodynia induced by intra-plantar carrageenan. All compounds had anti-nociceptive activity, but two of them showed faster and longer lasting analgesic effects than capsaicin. The present results suggest that TRPV1 agonists different from capsaicin could be used to develop topical analgesics with faster onset and more potent effects. © Copyright © 2020 Duarte, Cáceres, Sepúlveda, Arriagada, Olivares, Díaz-Franulic, Stehberg and González-Nilo. https://www.frontiersin.org/articles/10.3389/fphar.2020.01040/full

Bacterial infections are nowadays among the major threats to public health worldwide. Thus, there is an urgent and increased need for new antimicrobial agents. As a result, the exploration of the antimicrobial properties of different substances including ionic liquids (ILs) has recently attracted great attention. The present work is aimed at evaluating how the addition of halogens and hydrophobic substituents on alkylimidazolium units of ILs as well as the increase in their chain lengths affects the antimicrobial properties of such ILs. After their synthesis, the antibacterial activities of these compounds against Pseudomona aeruginosa, Escherichia coli, and Staphylococcus aureus are determined by measuring their minimal inhibitory concentrations (MICs). Key features in ILs-membrane interactions are also studied using long-term all-atom molecular dynamics simulations (MDs). The results show that these ILs have good antibacterial activity against S. aureus, E. coli, and P. aeruginosa, with MIC values range from7.81 to 62.50 μM. The antimicrobial property of tert-butyl N-methylphenolimidazolium salts (denoted as 8b and 8c) is particularly better with MIC values of 7.81 μM. The antibacterial efficacy is also found to depend on the alkyl chain length and substituents on the phenolic ring. Finally, MDs done for ILs in a phosphatidylcholine (POPC) bilayer show key features in the mechanism of IL-induced membrane disruption, where the ILs are inserted as clusters into one side of the bilayer until saturation is reached. This insertion increases "leaflet strain" up to critical threshold, likely triggering the morphological disruption of the membranes in the microbes.

Most of the computational tools involved in drug discovery developed during the 1980s were largely based on computational chemistry, quantitative structure-activity relationship (QSAR) and cheminformatics. Subsequently, the advent of genomics in the 2000s gave rise to a huge number of databases and computational tools developed to analyze large quantities of data, through bioinformatics, to obtain valuable information about the genomic regulation of different organisms. Target identification and validation is a long process during which evidence for and against a target is accumulated in the pursuit of developing new drugs. Finally, the drug delivery system appears as a novel approach to improve drug targeting and releasing into the cells, leading to new opportunities to improve drug efficiency and avoid potential secondary effects. In each area: target discovery, drug discovery and drug delivery, different computational strategies are being developed to accelerate the process of selection and discovery of new tools to be applied to different scientific fields. Research on these three topics is growing rapidly, but still requires a global view of this landscape to detect the most challenging bottleneck and how computational tools could be integrated in each topic. This review describes the current state of the art in computational strategies for target discovery, drug discovery and drug delivery and how these fields could be integrated. Finally, we will discuss about the current needs in these fields and how the continuous development of databases and computational tools will impact on the improvement of those areas. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

The tetrahydroquinoline ring system is a unit found in many biologically active natural products and pharmacologically relevant therapeutic agents. A new series of bistetrahydroquinolines (bis-THQs) was synthesized using imino Diels-Alder reactions between dialdehydes, anilines and N-vinyl-2-pyrrolidone (NVP). The notable features of this procedure are mild reaction conditions, greater selectivity and good yields of products. In addition, the inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) of some selected derivatives is reported. The feasible binding modes of these active compounds, within AChE and BuChE binding sites, were predicted by molecular docking experiments and their binding affinity was estimated by means of free energy calculations through the MM-GBSA approximation.

Due to the synthetic accessibility of different substituted coumarins and their biological properties, these heterocyclic compounds play an important role in the field of Medicinal Chemistry. In fact, coumarins have been previously described as anticancer, antiviral, anti-inflammatory, antimicrobial, enzymatic inhibitory and antioxidant agents. Within the field of neurodegenerative diseases are described different types and intervention processes, which include the development of acetylcholinesterase (AChE) inhibitors, which combined with another drugs are used on therapy for Alzheimer's diseases. These inhibitors allow acetylcholine levels in the brain to stabilize or even enhance them, since it's established that this enzyme is responsible for the metabolism of this important neurotransmitter. In our group, we have already synthesised multiple novel compounds incorporating the coumarin moiety with remarkable activity towards MAO and/or AChE. In this work, we continue to exploit this scaffold by the synthesis of novel 3-amidocoumarins for the treatment of neurodegenerative diseases. Following this work, pharmacological studies of the prepared compounds as AChE inhibitors are currently in progress. Some preliminary results are presented in this communication.

Nitrogen heterocycles are a part of a special group of organic substances due to its many applications in the pharmaceutical market, exist a large number of structures carrying nitrogenous substances. Among these heterocycles the isoxazoles and tetrahydroquinolines (THQs)1 have shown significant biological activity on different therapeutic targets. They show several applications in diverse areas such as pharmaceuticals, agrochemistry, and industry.2 They are also found in natural sources showing insecticidal, plant growth regulation, and pigment functions.3 Within the field of activity of the heterocycles is found the antibacterial activity, which has had a growing interest because the inappropriated use of antibiotic has increased the resistance of bacterial to the commercial antibiotics, even the appearance of bacterial strain with no treatment knows.4 Similarly, the emergence of antibiotic resistance in some bacterial populations is yet a relevant field of study in some areas of Science included the organic chemistry.Due to mentioned previously, the THQs e isoxazole compounds have been considered a good starting material for the search of novel antimicrobial agents, therefore we include them in this research.Isoxazoles derivatives were synthesized by 1,3 dipolar cycloaddition and a serie of tetrahydroquinolines derivatives were synthesized by Povarov reaction, these compounds were purified by conventional chromatographic techniques and characterized spectroscopically. Antibacterial activity was assessed by spectrophotometric measurements, determining the MIC for each compound against the four bacterial, Escherichia coli, Pseudomona aeruginosa, Staphylococcus aureus and Acinetobacter baumannii.

C26H20N2O2, monoclinic, C2/c (no. 15), a = 36.237(2) Å, b = 6.6915(3) Å, c = 16.3951(8) Å, β = 107.453(4)°, V = 3792.5 Å3, Z = 8, Rgt(F) = 0.0686, wRref(F2) = 0.1991, T = 173 K.