In Silico Approach: Anti-Tuberculosis Activity of Caespitate in the H37Rv Strain.

Tuberculosis is a highly lethal bacterial disease worldwide caused by Mycobacterium tuberculosis (Mtb). Caespitate is a phytochemical isolated from Helichrysum caespititium, a plant used in African traditional medicine that shows anti-tubercular activity, but its mode of action remains unknown. It is suggested that there are four potential targets in Mtb, specifically in the H37Rv strain: InhA, MabA, and UGM, enzymes involved in the formation of Mtb's cell wall, and PanK, which plays a role in cell growth. Two caespitate conformational structures from DFT conformational analysis in the gas phase (GC) and in solution with DMSO (CS) were selected. Molecular docking calculations, MM/GBSA analysis, and ADME parameter evaluations were performed. The docking results suggest that CS is the preferred caespitate conformation when interacting with PanK and UGM. In both cases, the two intramolecular hydrogen bonds characteristic of caespitate's molecular structure were maintained to achieve the most stable complexes. The MM/GBSA study confirmed that PanK/caespitate and UGM/caespitate were the most stable complexes. Caespitate showed favorable pharmacokinetic characteristics, suggesting rapid absorption, permeability, and high bioavailability. Additionally, it is proposed that caespitate may exhibit antibacterial and antimonial activity. This research lays the foundation for the design of anti-tuberculosis drugs from natural sources, especially by identifying potential drug targets in Mtb.

L-Citrullinato-Bipyridine and L-Citrullinato-Phenanthroline Mixed Copper Complexes: Synthesis, Characterization and Potential Anticancer Activity.

Citrulline (C6H13N3O3) is an amino acid found in the body as a zwitterion. This means its carboxylic and amine groups can act as Lewis donors to chelate metal cations. In addition, citrulline possesses a terminal ureido group on its aliphatic chain, which also appears to coordinate. Here, two new mixed complexes of citrulline were made with 1,10-phenanthroline and 2,2'-bipyridine. These compounds, once dissolved in water, gave aquo-complexes that were subject to DFT studies and in vitro toxicity studies on cancer cell lines (HeLa, MDA-MB-231, HCT 15, and MCF7) showed promising results. Docking studies with DNA were also conducted, indicating potential anticancer properties.

Structural Basis of the Binding Mode of the Antineoplastic Compound Motixafortide (BL-8040) in the CXCR4 Chemokine Receptor.

Modulation of the CXCL12-CXCR4 signaling axis is of the utmost importance due to its central involvement in several pathological disorders, including inflammatory diseases and cancer. Among the different currently available drugs that inhibit CXCR4 activation, motixafortide-a best-in-class antagonist of this GPCR receptor-has exhibited promising results in preclinical studies of pancreatic, breast, and lung cancers. However, detailed information on the interaction mechanism of motixafortide is still lacking. Here, we characterize the motixafortide/CXCR4 and CXCL12/CXCR4 protein complexes by using computational techniques including unbiased all-atom molecular dynamics simulations. Our microsecond-long simulations of the protein systems indicate that the agonist triggers changes associated with active-like GPCR conformations, while the antagonist favors inactive conformations of CXCR4. Detailed ligand-protein analysis indicates the importance of motixafortide's six cationic residues, all of which established charge-charge interactions with acidic CXCR4 residues. Furthermore, two synthetic bulky chemical moieties of motixafortide work in tandem to restrict the conformations of important residues associated with CXCR4 activation. Our results not only elucidate the molecular mechanism by which motixafortide interacts with the CXCR4 receptor and stabilizes its inactive states, but also provide essential information to rationally design CXCR4 inhibitors that preserve the outstanding pharmacological features of motixafortide.

Interaction of copper potential metallodrugs with TMPRSS2: A comparative study of docking tools and its implications on COVID-19.

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. For the virus to enter the host cell, its spike (S) protein binds to the ACE2 receptor, and the transmembrane protease serine 2 (TMPRSS2) cleaves the binding for the fusion. As part of the research on COVID-19 treatments, several Casiopeina-analogs presented here were looked at as TMPRSS2 inhibitors. Using the DFT and conceptual-DFT methods, it was found that the global reactivity indices of the optimized molecular structures of the inhibitors could be used to predict their pharmacological activity. In addition, molecular docking programs (AutoDock4, Molegro Virtual Docker, and GOLD) were used to find the best potential inhibitors by looking at how they interact with key amino acid residues (His296, Asp 345, and Ser441) in the catalytic triad. The results show that in many cases, at least one of the amino acids in the triad is involved in the interaction. In the best cases, Asp435 interacts with the terminal nitrogen atoms of the side chains in a similar way to inhibitors such as nafamostat, camostat, and gabexate. Since the copper compounds localize just above the catalytic triad, they could stop substrates from getting into it. The binding energies are in the range of other synthetic drugs already on the market. Because serine protease could be an excellent target to stop the virus from getting inside the cell, the analyzed complexes are an excellent place to start looking for new drugs to treat COVID-19.

Conceptual DFT, QTAIM, and Molecular Docking Approaches to Characterize the T-Type Calcium Channel Blocker Anandamide.

The anandamide is a relevant ligand due to its capacity of interacting with several proteins, including the T-type calcium channels, which play an important role in neuropathic pain and depression disorders. Hence, a detailed characterization of the chemical properties and conformational stability of anandamide may provide valuable information to understand its behavior in a biological context. Herein, conceptual DFT and QTAIM analyses were performed to theoretically characterize the chemical reactivity properties and the structural stability of conformations of anandamide, using the BP86/cc-pVTZ level of theory. Global reactivity description, based on conceptual DFT, indicates that the hardness increases and the electrophilicity index decreases for both, the hairpin and U-shape conformers relative to the extended conformers. Also, an increase in the chemical potential value and a decrease in the electronegativity and the electrophilicity index is observed in the ethanolamide open ring conformers in comparison with the corresponding closed ring structures. In addition, regarding the characterization of local reactivity descriptors, the maximum values of the Fukui and Parr functions indicate that the most probable location for a nucleophilic attack is either the hydroxyl oxygen located in the ethanolamide closed ring conformers or the carbonyl oxygen present in the open ring conformers. The most probable location for an electrophilic attack is in the alkyl double bond region in all anandamide conformers. According to the QTAIM results, the intramolecular hydrogen bond formation stabilizing the structure of anandamide has interaction energy values for the closed ring conformations of 12.33-12.46 kcal mol-1, indicating a strong interaction. Lastly, molecular docking calculations determined that a region in the pore, denominate as pore-blocking, is a probable site for the interaction of anandamide with the human Cav3.2 isoform of the T-type calcium channel family. The pore-blocking site contains hydrophobic residues where the non-polar part in the final alkyl region of anandamide established mainly alkyl-alkyl interactions, while the polar part (the ethanolamide group) interacts with the polar residue S900. The information based on conceptual DFT presented may aid in the design of drugs with similar chemical characteristics as those identified in anandamide so as to bind anandamide-interacting proteins, including the T-type calcium channels.

Tris(2-Pyridylmethylamine)V(O)2 Complexes as Counter Ions of Diprotonated Decavanadate Anion: Potential Antineoplastic Activity.

The synthesis and theoretical-experimental characterization of a novel diprotanated decavanadate is presented here due to our search for novel anticancer metallodrugs. Tris(2-pyridylmethyl)amine (TPMA), which is also known to have anticancer activity in osteosarcoma cell lines, was introduced as a possible cationic species that could act as a counterpart for the decavanadate anion. However, the isolated compound contains the previously reported vanadium (V) dioxido-tpma moieties, and the decavanadate anion appears to be diprotonated. The structural characterization of the compound was performed by infrared spectroscopy and single-crystal X-ray diffraction. In addition, DFT calculations were used to analyze the reactive sites involved in the donor-acceptor interactions from the molecular electrostatic potential maps. The level of theory mPW1PW91/6-31G(d)-LANL2DZ and ECP = LANL2DZ for the V atom was used. These insights about the compounds' main interactions were supported by analyzing the noncovalent interactions utilizing the AIM and Hirshfeld surfaces approach. Molecular docking studies with small RNA fragments were used to assess the hypothesis that decavanadate's anticancer activity could be attributed to its interaction with lncRNA molecules. Thus, a combination of three potentially beneficial components could be evaluated in various cancer cell lines.

Theoretical Study of the Structural Stability, Chemical Reactivity, and Protein Interaction for NMP Compounds as Modulators of the Endocannabinoid System.

The cannabinoid receptors (CB1/CB2) and the T-type calcium channels are involved in disorders associated with both physiological pain and depressive behaviors. Valuable pharmacological species carbazole derivatives such as the NMP-4, NMP-7, and NMP-181 (Neuro Molecular Production) regulate both biological entities. In this work, DFT calculations were performed to characterize theoretically their structural and chemical reactivity properties using the BP86/cc-pVTZ level of theory. The molecular orbital contributions and the chemical reactivity analysis reveal that a major participation of the carbazole group is in the donor-acceptor interactions of the NMP compounds. The DFT analysis on the NMP compounds provides insights into the relevant functional groups involved during the ligand-receptor interactions. Molecular docking analysis is used to reveal possible sites of interaction of the NMP compounds with the Cav3.2 calcium channel. The interaction energy values and reported experimental evidence indicate that the site denominated as "Pore-blocking", which is formed mainly by hydrophobic residues and the T586 residue, is a probable binding site for the NMP compounds.

Volatile Organic Compounds Produced by Cacao Endophytic Bacteria and Their Inhibitory Activity on Moniliophthora roreri.

Several studies have reported that bacteria produce anti-fungal volatiles. We identified the organic volatile compounds produced by six cacao endophytic bacteria (CEB) strains (Bacillus amyloliquefaciens CFFSUR-B35, Bacillus megaterium CFFSUR-B32, Bacillus muralis CFFSUR-B39, Bacillus pumilus CFFSUR-B34, Bacillus subtilis CFFSUR-B31, and Novosphingobium lindaniclasticum CFFSUR-B36). We evaluated their inhibitory effect on mycelium growth and spore germination of the phytopathogenic fungus Moniliophtora roreri. The volatiles produced by these six CEB, were collected and identified by SPME and GC-MS. Moreover, the inhibitory effect of five synthetic volatile organic compounds, individually and in mixtures (dimethyl disulfide, 2-5 dimethyl pyrazine, α-pinene, 2-heptanone and 2-ethyl hexanol) on M. roreri mycelium growth and spore germination was evaluated. All strains examined produced volatiles in different amounts; 13 to 10 compounds were identified, including sulfide, alcohol benzene derivate, pyrazine, ketone, nitrogen and terpene compounds. The B. subtilis CFFSUR-B31 strain produced the largest number of volatiles, while B. pumilus CFFSUR-B34 produced the fewest and the lowest amounts. The volatile organic compounds produced by B. pumilus CFFSUR-B34, B. muralis CFFSUR-B39 and N. lindaniclasticum CFFSUR-B36 inhibited M. roreri mycelium growth by more than 35%, sporulation by more than 81% and spore germination by more than 74%. However, when synthetic compounds were evaluated individually and in mixtures, 2-ethyl hexanol at 100,000 ppm (20 mg/filter paper disc) inhibited M. roreri mycelium growth by 100%, followed by organic volatile compound mixtures C (dimethyl disulfide, 2,5-dimethyl pyrazine, α-pinene, 2-ethyl-hexanol, 2-Heptanone) and D (only the top four) at 100,000 ppm (4 and 5 mg/filter paper disc) which inhibited spore germination by 97 and 89%, respectively.

Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment.

Transition metal-based compounds have shown promising uses as therapeutic agents. Among their unique characteristics, these compounds are suitable for interaction with specific biological targets, making them important potential drugs to treat various diseases. Copper compounds, of which Casiopeinas® are an excellent example, have shown promising results as alternatives to current cancer therapies, in part because of their intercalative properties with DNA. Vanadium compounds have been extensively studied for their pharmacological properties and application, mostly in diabetes, although recently, there is a growing interest in testing their activity as anti-cancer agents. In the present work, two compounds, [Cu(Metf)(bipy)Cl]Cl·2H2O and [Cu(Impy)(Gly)(H2O)]VO3, were obtained and characterized by visible and FTIR spectroscopies, single-crystal X-ray diffraction, and theoretical methods. The structural and electronic properties of the compounds were calculated through the density functional theory (DFT) using the Austin-Frisch-Petersson functional with dispersion APFD, and the 6-311 + G(2d,p) basis set. Non-covalent interactions were analyzed using Hirshfeld surface analysis (HSA) and atom in molecules analysis (AIM). Additionally, docking analysis to test DNA/RNA interactions with the Casiopeina-like complexes were carried out. The compounds provide metals that can interact with critical biological targets. In addition, they show interesting non-covalent interactions that are responsible for their supramolecular arrangements.

Analysis of the Gas Phase Acidity of Substituted Benzoic Acids Using Density Functional Concepts.

A theoretical study of the effect of the substituent Z on the gas phase acidity of substituted benzoic acids ZC6H4COOH in terms of density functional theory descriptors (chemical potential, softness and Fukui function) is presented. The calculated gas phase ΔacidG° values obtained were close to the experimental ones reported in the literature. The good relationship between the ΔacidG° values and the electronegativity of ZC6H4COOH and its fragments, suggested a better importance of the inductive than polarizability contributions. The balance of inductive and resonance contributions of the substituent in the acidity of substituted benzoic acids showed that the highest inductive and resonance effects were for the -SO2CF3 and -NH2 substituents in the para- and ortho-position, respectively. The Fukui function confirmed that the electron-releasing substituent attached to the phenyl ring of benzoic acid decreased the acidity in the trend ortho > meta > para, and the electron-withdrawing substituent increased the acidity in the trend ortho < meta < para.

Oxidovanadium(V) complexes as promising anticancer photosensitizers.

Photodynamic therapy (PDT) is an alternative treatment widely used against cancer. PDT requires molecular systems, known as photosensitizers (PS), which not only exhibit strong absorption at a particular wavelength range, but also need to be selectively accumulated inside cancer cells. PS are activated by specific wavelengths that cause tumor cell death by mechanisms related with oxidative stress. In this paper, three oxidovanadium(V) complexes linked to a Schiff base, which exhibit anticancer activity by displaying desirable accumulation inside malignant cells, are studied using Density Functional Theory (DFT) and Time Dependent-DFT (TD-DFT) methodologies to characterize their structural and photophysical properties as possible PS. The maximum absorption of these complexes in aqueous solution was predicted to be approximately 460 nm presenting a ligand-to-metal charge transfer. Additionally, we describe the photodynamic type reaction that these complexes can undergo when considered as PS candidates. Our results suggest that the system, containing triethylammonium as substituent, is the most suitable complex to act both as PS and as a possible therapeutic candidate in PDT.

Experimental and DFT Study of the Photoluminescent Green Emission Band of Halogenated (-F, -Cl, and -Br) Imines.

The morphological, optical, and structural changes in crystalline chiral imines derived from 2-naphthaldehyde as a result of changing the -F, -Cl, and -Br halogen (-X) atoms are reported. Scanning electron microscopy (SEM), optical absorption, photoluminescence (PL), and powder X-ray diffraction (XRD) studies were performed. Theoretical results of optical and structural properties were calculated using the PBE1PBE hybrid functional and compared with the experimental results. Differences in surface morphology, absorbance, XRD, and PL of crystals were due to the change of halogen atoms in the chiral moiety of the imine. Absorption spectra exhibited the typical bands of the naphthalene chromophore located in the ~200-350 nm range. Observed absorption bands in the UV region are associated with π→π* and n→π* electronic transitions. The band gap energy was calculated using the Tauc model. It showed a shift in the ~3.5-4.5 eV range and the crystals exhibited different electronic transitions associated with the results of absorbance in the UV region. XRD showed the monoclinic→orthorhombic crystalline phase transition. PL spectra displayed broad bands in the visible region and all the samples have an emission band (identified as a green emission band) in the ~400-750 nm range. This was associated with defects produced in the morphology, molecular packing, inductive effect and polarizability, crystalline phase transition, and increase in size of the corresponding halogen atoms; i.e., changes presumably induced by -C-X…X-, -C-X…N-, -C-N…π, and -C-X…π interactions in these crystalline materials were associated with morphological, optical, and structural changes.

Inhibitory mechanism of 17ß-aminoestrogens in the formation of Aß aggregates.

Alzheimer's disease (AD) is a complex neurodegenerative disorder associated with the aggregation of the amyloid-beta peptide (Aß) into large oligomers and fibrils that damage healthy brain cells. The predominant peptide fragments in the plaques are mainly formed by the Aß1-40 and Aß1-42 peptides, albeit the eleven-residue Aß25-35 segment is largely used in biological studies because it retains the neurotoxic properties of the longer Aß peptides. Recent studies indicate that treatment with therapeutic steroid hormones reduces the progress of the disease in AD models. Particularly, treatment with 17ß-aminoestrogens (AEs) has shown a significant alleviation of the AD development by inhibiting oxidative stress and neuronal death. Yet, the mechanism by which the AE molecules exhibit their beneficial effects remains speculative. To shed light into the molecular mechanism of inhibition of the AD development by AEs, we investigated the possibility of direct interaction with the Aß25-35 peptide. First, we calculate various interacting electronic properties of three AE derivatives as follows: prolame, butolame, and pentolame by performing DFT calculations. To account for the polymorphic nature of the Aß aggregates, we considered four different Aß25-35 systems extracted from AD relevant fibril structures. From the calculation of different electron density properties, specific interacting loci were identified that guided the construction and optimization of various complexes. Interestingly, the results suggest a similar inhibitory mechanism based on the direct interaction between the AEs and the M35 residue that seems to be general and independent of the polymorphic properties of the Aß aggregates. Our analysis of the complex formation provides a structural framework for understanding the AE therapeutic properties in the molecular inhibitory mechanism of Aß aggregation.

[Tratamiento quirúrgico de la escoliosis idiopática del adolescente. Resultados en el Instituto Nacional de Rehabilitación de México. Seguimiento mínimo de 24 meses]. / Idiopathic scoliosis's surgical treatment. Results in Mexico's National Rehabilitation Institute. 24 months follow.

ANTECEDENTES: La escoliosis idiopática del adolescente se define como una deformidad tridimensional de la columna vertebral que se presenta entre los 10 y los 18 años, y que se manifiesta con una curvatura vertebral en el plano coronal mayor de 10°. Esta deformidad afecta al 2-3% de la población general, pero solo el 10% del total requerirá en algún momento tratamiento quirúrgico. El método de elección para el manejo es el uso de tornillos transpediculares y barras desrotadoras. OBJETIVO: Realizar un análisis descriptivo de los pacientes que recibieron manejo quirúrgico en nuestro instituto con tornillos transpediculares y barras. MÉTODO: Se trata de un estudio observacional, retrospectivo, analítico, abierto, de muestreo no probabilístico, en el que se incluyeron los pacientes tratados con manejo quirúrgico entre 2012 y 2013. Las deformidades se estratificaron de acuerdo con la clasificación de Lenke. El ángulo de corrección de la deformidad, los niveles instrumentados, el sangrado transquirúrgico y la presencia de complicaciones fueron las variables analizadas. RESULTADOS: La mayoría de los pacientes presentaron curvas Lenke IBN, Nash Moe III, Cobb un promedio de 59.4° y cifosis de 47.8. En promedio se siguió a los pacientes por 35.84 meses, detectando un aumento de la curvatura coronal de 2.28° y un aumento de la curvatura sagital de 2.8°. CONCLUSIÓN: Al comparar estos resultados y la literatura mundial se concluyó que el tratamiento de la escoliosis idiopática del adolescente es un método seguro y reproducible que ofrece una mayor ventaja biomecánica y biológica sobre el uso de instrumentación mixta utilizada anteriormente. BACKGROUND: Adolescent's idiopathic scoliosis is defined as a three-dimensional deformity of the spine, which occurs between 10 and 18-year-old, has a spinal curvature >10° in the coronal plane. This deformity affects 2­3% of the general population, however, only 10% of the total will require surgery at some point. The method of choice for management is the use of pedicle screws and rods derotational. OBJECTIVE: To perform a descriptive analysis of patients who received surgical treatment in our institute with pedicle screws and rods. METHODS: This is an observational, retrospective, analytical, open study, non-probability sampling, in which patients requiring surgical treatment at our institute between 2012 and 2013 were included, the deformities were stratified according to the classification of Lenke. The angle of deformity correction, instrumented levels, amount of bleeding, presence of complications were the variables analyzed. RESULTS: Lenke classifying mostly IBN, Moe Nash III, an average of 59.4° Cobb and kyphosis of 47.8. On average it was followed patients for 35.84 months, detecting an increase 2.28° coronal curvature and sagittal curvature increase of 2.8°. CONCLUSION: Comparing these results and world literature concluded that the treatment of adolescent's idiopathic scoliosis is a safe and reproducible method that provides greater biomechanical and biological advantage over the use of mixed instrumentation used previously.

Pharmacological and Toxicological Threshold of Bisammonium Tetrakis 4-(N,N-Dimethylamino)pyridinium Decavanadate in a Rat Model of Metabolic Syndrome and Insulin Resistance.

Vanadium(IV/V) compounds have been studied as possible metallopharmaceutical drugs against diabetes mellitus. However, mechanisms of action and toxicological threshold have been tackled poorly so far. In this paper, our purposes were to evaluate the metabolic activity on dyslipidemia and dysglycemia, insulin signaling in liver and adipose tissue, and toxicology of the title compound. To do so, the previously reported bisammonium tetrakis 4-(N,N-dimethylamino)pyridinium decavanadate, the formula of which is [DMAPH]4(NH4)2[V10O28]·8H2O (where DMAPH is 4-dimethylaminopyridinium ion), was synthesized, and its dose-response curve on hyperglycemic rats was evaluated. A Long-Evans rat model showing dyslipidemia and dysglycemia with parameters that reproduce metabolic syndrome and severe insulin resistance was generated. Two different dosages, 5 µmol and 10 µmol twice a week of the title compound (equivalent to 2.43 mg·V/kg/day and 4.86 mg·V/kg/day, resp.), were administered intraperitoneal (i.p.) for two months. Then, an improvement on each of the following parameters was observed at a 5 µmol dose: weight reduction, abdominal perimeter, fatty index, body mass index, oral glucose tolerance test, lipid profile, and adipokine and insulin resistance indexes. Nevertheless, when the toxicological profile was evaluated at a 10 µmol dose, it did not show complete improvement, tested by the liver and adipose histology, as well as by insulin receptor phosphorylation and GLUT-4 expression. In conclusion, the title compound administration produces regulation on lipids and carbohydrates, regardless of dose, but the pharmacological and toxicological threshold for cell regulation are suggested to be up to 5 µmol (2.43 mg·V/kg/day) dose twice per week.

Bulk Modification of Poly(lactide) (PLA) via Copolymerization with Poly(propylene glycol) Diglycidylether (PPGDGE).

Copolymers of l-lactide and poly(propylene glycol) diglycidyl ether (PPGDGE380) were synthesized by ring opening polymerization (ROP). Stannous octoate was used as the catalyst and 1-dodecanol as the initiator. The effect of the variables on the thermal properties of the copolymers was investigated by differential scanning calorimetry (DSC). Contact angle measurements were made in order to study the wettability of the synthesized copolymers. The copolymers differed widely in their physical characteristics, ranging from weak elastomers to tougher thermoplastics, according to the ratio of l-lactide and PPGDGE380. The results showed that the copolymers were more hydrophilic than neat Poly(lactide) (PLA) and the monomer ratio had a strong influence on the hydrophilic properties.

Cis-trans isomerism in a square-planar platinum(II) complex bearing bulky fluorinated phosphane ligands.

Transition-metal complexes bearing fluorinated phosphane and thiolate ligands has been an area of study in recent years and the chemical context of the current work is related to the metal-assisted functionalization of fluorinated derivatives. The cis and trans isomers of the square-planar complex bis[(pentafluorophenyl)diphenylphosphane-κP]bis(2,3,5,6-tetrafluorobenzenethiolato-κS)platinum(II), [Pt(C6HF4S)2{P(C6H5)2(C6F5)}2], have been crystallized from a single chromatographic fraction and characterized by X-ray diffraction analysis. The stabilization of the cis isomer results from weak intramolecular π-stacking interactions and possibly from the formation of a C-F...Pt contact, characterized by an F...Pt separation of 2.957 (6) Å. The natural bond orbital analysis (NBO) for this isomer confirms that the corresponding F → Pt charge transfer accounts for 6.92 kcal mol(-1) in the isomer stabilization. Such interactions are not present in the centrosymmetric trans isomer.

Antioxidative stress effect of epicatechin and catechin induced by Aß25-35 in rats and use of the electrostatic potential and the Fukui function as a tool to elucidate specific sites of interaction.

Alzheimer's disease (AD) is a neurodegenerative disorder caused by the aggregation of the amyloid-beta peptide (Aß) in senile plaques and cerebral vasculature. The Aß25-35 fraction has shown the most toxicity; its neurotoxic mechanisms are associated with the generation of oxidative stress and reactive astrogliosis that induce neuronal death and memory impairment. Studies indicate that pharmacological treatment with flavonoids reduces the rate of AD, in particular, it has been shown that antioxidants are compounds that could interact with this peptide due to their antioxidant proprieties. In this study, experimental and computational tools were used to calculate the molecular electrostatic potential and the Fukui function with the Gaussian 09 computational program, to predict the most reactive parts of these molecules and make the complex between Aß25-35 and two flavonoids (catechin and epicatechin) in the absolute gas-phase, where a possible interaction between them was observed. This is important for understanding the Aß25-35-Flavonoid (A-F) interaction as a therapeutic strategy to inhibit the neurotoxic effects that this peptide causes in AD, which currently is still considered an ambiguous process.

Antifungal performance of extracellular chitinases and culture supernatants of Streptomyces galilaeus CFFSUR-B12 against Mycosphaerella fijiensis Morelet.

The tropical and mycoparasite strain Streptomyces galilaeus CFFSUR-B12 was evaluated as an antagonist of Mycosphaerella fijiensis Morelet, causal agent of the Black Sigatoka Disease (BSD) of banana. On zymograms of CFFSUR-B12 culture supernatants, we detected four chitinases of approximately 32 kDa (Chi32), 20 kDa (Chi20), and two with masses well over 170 kDa (ChiU) that showed little migration during denaturing electrophoresis at different concentrations of polyacrylamide. The thymol-sulphuric acid assay showed that the ChiU were glycosylated chitinases. Moreover, matrix assisted laser desorption ionization time-of-flight MS analysis revealed that the ChiU are the same protein and identical to a family 18 chitinase from Streptomyces sp. S4 (gi|498328075). Chi32 was similar to an extracellular protein from Streptomyces albus J1074 (gi|478687481) and Chi20 was non-significantly similar to chitinases from five different strains of Streptomyces (P > 0.05). Subsequently, Chi32 and Chi20 were partially purified by anion exchange and hydrophobic interaction chromatography and tested against M. fijiensis. Chitinases failed to inhibit ascospore germination, but inhibited up to 35 and 62% of germ tube elongation and mycelial growth, respectively. We found that crude culture supernatant and living cells of S. galilaeus CFFSUR-B12 were the most effective in inhibiting M. fijiensis and are potential biocontrol agents of BSD.

Epimerization of C-22 in (25R)- and (25S)-sapogenins.

Most of the naturally occurring steroidal sapogenins (C-23 non-substituted frameworks), possess an R configuration at the spiro C-22 center. Their C-22 epimers have become important targets in biological research. This paper describes a procedure to obtain 22S-spirostans from 22R-sapogenins and pseudosapogenin skeletons, without affecting the chirality at either C-25 or C-20. An optimal way to synthesize the pair of C-22 stereoisomers of 23-acetyldiosgenin is also reported. The latter was obtained from a 22,26-epoxycholestane or from 23-acetylfurostene compounds.