Search Results (17)

The World Health Organization notes that some bacteria have been demonstrated to possess significant public health risks; they have antibiotic resistance, and there are fewer alternatives for control. The n-hexane extract and cinaguaiacin obtained from Artemisia cina show promising antibacterial activity, including against multidrug-resistant bacteria that affect animal and human health. Objective: The aim of this study was to determine the antibacterial activity of the n-hexane extract of A. cina and cinaguaiacin against multidrug-resistant bacteria. Methods:A. cina was collected in the pre-flowering period, the n-hexane extract was obtained, and chromatographic techniques and structure were used to separate the lignans, which were elucidated with nuclear magnetic resonance techniques. Four ATCC strains were used, and four strains were isolated from clinical cases with different resistance profiles. The antibacterial activity was determined by calculating the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), the time-kill kinetics assay, and the cell membrane integrity and DNA release assay. Molecular docking studies of lignans demonstrated the binding mode involved in the active site of DNA gyrase B. Results: The n-hexane extract inhibited growth against 87.5% of the strains tested (MIC 5.31 to 42.5 mg/mL) and showed bactericidal activity against 25% of the strains tested (MBC 0.62 to 85 mg/mL). Cinaguaiacin inhibited growth against 100% of the strains tested (MIC, 0.56 to 2.25 mg/mL) and exhibited bactericidal activity against 25% of the strains tested (MBC, 0.62 to 85 mg/mL). Conclusions: The mechanism of cinaguaiacin’s action may be associated with damage to the plasma membrane, as the protein and DNA levels were higher than those of the positive control. The n-hexane extract and cinaguaiacin obtained from A. cina showed a bacteriostatic or bactericidal effect, depending on the strain evaluated. Full article

Alzheimer’s disease (AD) represents a significant challenge among neurodegenerative disorders, as effective treatments and therapies remain largely undeveloped. Despite extensive research efforts employing various methodologies and diverse genetic models focused on amyloid-β (Aβ) pathology, the research for effective therapeutic strategies remains inconclusive. The key pathological features of AD include Aβ senile plaques, neurofibrillary tangles (NFTs), and the activation of neuroinflammatory pathways. Presently, investigations into AD and assessing potential treatments predominantly utilize Aβ transgenic models. Conversely, non-transgenic models may provide valuable insights into the multifaceted pathological states associated with AD. Thus, these models may serve as practical complementary tools for evaluating therapeutic and intervention strategies, since the primary AD risk factors are most frequently modeled. This review aims to critically assess the existing literature on AD non-transgenic models induced by streptozotocin, scopolamine, aging, mechanical stress, metals, and dietary patterns to enhance their application in AD research. Full article

After attending both the “Decade to Educate in the Sustainable Development and the Agenda 30 of the UNESCO” and the “ACS GCI Pharmaceutical Roundtable”, which focused on sustainable chemistry, in this article, a green chemistry contribution to the Kamal Qureshi protocol is offered; thus, DIM^® and several of its analogs (3,3′-diindolylmethanes) were suitably produced under the green chemistry protocol. In the first stage, the substrate indol-3-yl carbinol was evaluated using mechanochemistry (the best mode) in comparison to other activating methods (near-infrared and microwave electromagnetic irradiation and ultrasound), wishing to highlight the employment of both TAFF^®, an excellent and well-characterized natural catalyst (bentonitic clay), and acetone, a green solvent, in addition to the analysis of the procedures in real-time. In the second stage, the mechanochemical methodology was extended to produce a set of fifteen DIMs, in the last stage, the use of a green metric exhibited the greenness of the approach, with it being important to highlight that, to our knowledge, after a search in the literature, this is the first time that the process has been evaluated to demonstrate its greenness. Full article

Background/Objectives: Breast cancer is a disease with a high mortality rate worldwide; consequently, urgent achievements are required to design new greener drugs, leaving natural products and their derivatives as good options. A constant antineoplastic effect has been observed when the phytoproduct contains an indole fragment. Methods: Therefore, the objective of this work was to carry out a thoughtful computational study to perform an appropriate evaluation of four novel molecules of the class of the 3-indolylquinones as phytodrug candidates for antineoplastic activity: thymoquinone (TQ), 2,6-dimethoxy-1,4-benzoquinone (DMQ), 2,3-dimethoxy-5-methyl-1,4-benzoquinone (DMMQ), and 2,5-dihydroxy-1,4-benzoquinone (DHQ). It is important to highlight that the obtained computational results of the target compounds were compared-correlated with the theoretical and experimental literature data previously reported of several indolylquinones: indolylperezone, indolylisoperezone, indolylmenadione, and indolylplumbagin (IE-IH, respectively). Results: The results revealed that the studied structures possibly presented antineoplastic activity, in addition to the fact that the reactivity parameters showed that two of the evaluated compounds have the option to present IC₅₀ values lower than or similar to 25 mg/mL, activity like that of indolylisoperezone; moreover, they show molecular coupling to PARP-1. Finally, the prediction of the calculated physicochemical parameters coincides with the Lipinski and Veber rules, indicating that the adsorption, metabolism, and toxicity parameters are acceptable for the studied compounds, obtaining high drug score values. Conclusions: Finally, a comparison between the proposed molecules and others previously synthesized was appropriately performed, establishing that the synthesis of the studied compounds and the determination of their pharmacological properties in an experimental manner are of interest. Full article

The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor. Full article

Poly-ADP-Ribose Polymerase (PARP-1) is an overexpressed enzyme in several carcinomas; consequently, the design of PARP-1 inhibitors has acquired special attention. Hence, in the present study, three compounds (8–10) were produced through a Michael addition protocol, using phenylmethanethiol, 5-fluoro-2-mercaptobenzyl alcohol, and 4-mercaptophenylacetic acid, respectively, as nucleophiles and perezone as the substrate, expecting them to be convenient candidates that inhibit PARP-1. It is convenient to note that in the first stage of the whole study, the molecular dynamics (MD) simulations and the quantum chemistry studies of four secondary metabolites, i.e., perezone (1), perezone angelate (2), hydroxyperezone (3), and hydroxyperezone monoangelate (4), were performed, to investigate their interactions in the active site of PARP-1. Complementarily, a docking study of a set of eleven sulfur derivatives of perezone (5–15) was projected to explore novel compounds, with remarkable affinity to PARP-1. The molecules 8–10 provided the most adequate results; therefore, they were evaluated in vitro to determine their activity towards PARP-1, with 9 having the best IC₅₀ (0.317 µM) value. Additionally, theoretical calculations were carried out using the density functional theory (DFT) with the hybrid method B3LYP with a set of base functions 6-311++G(d,p), and the reactivity properties were compared between the natural derivatives of perezone and the three synthesized compounds, and the obtained results exhibited that 9 has the best properties to bind with PARP-1. Finally, it is important to mention that 9 displays significant inhibitory activity against MDA-MB-231 and MCF-7 cells, i.e., 145.01 and 83.17 µM, respectively. Full article

To aid the possible prevention of multidrug resistance in tumors and cause lower toxicity, a set of sixteen novel dihydropyridine carboxylic acids derivatives 3a–p were produced; thus, the activation of various ynones with triflic anhydride was performed, involving a nucleophilic addition of several bis(trimethylsilyl) ketene acetals, achieving good yields requiring easy workup. The target molecules were unequivocally characterized by common spectroscopic methods. In addition, two of the tested compounds (3a, and 3b) were selected to perform in silico studies due to the highest cytotoxic activity towards the HCT-15 cell line (7.94 ± 1.6 μM and 9.24 ± 0.9 μM, respectively). Employing theoretical calculations with density functional theory (DFT) using the B3LYP/6-311++G(d,p) showed that the molecular parameters correlate adequately with the experimental results. In contrast, predictions employing Osiris Property Explorer showed that compounds 3a and 3b present physicochemical characteristics that would likely make it an orally active drug. Moreover, the performance of Docking studies with proteins related to the apoptosis pathway allowed a proposal of which compounds could interact with PARP-1 protein. Pondering the obtained results (synthesis, in silico, and cytotoxic activity) of the target compounds, they can be judged as suitable antineoplastic agent candidates. Full article

Three novel biomaterials obtained via inclusion complexes of β–cyclodextrin, 6-deoxi-6-amino-β–cyclodextrin and epithelial growth factor grafted to 6-deoxi-6-amino-β–cyclodextrin with polycaprolactone. Furthermore, some physicochemical, toxicological and absorption properties were predicted using bioinformatics tools. The electronic, geometrical and spectroscopical calculated properties agree with the properties obtained via experimental methods, explaining the behaviors observed in each case. The interaction energy was obtained, and its values were −60.6, −20.9 and −17.1 kcal/mol for β–cyclodextrin/polycaprolactone followed by the 6-amino-β–cyclodextrin-polycaprolactone complex and finally the complex of epithelial growth factor anchored to 6-deoxy-6-amino–β–cyclodextrin/polycaprolactone. Additionally, the dipolar moments were calculated, achieving values of 3.2688, 5.9249 and 5.0998 Debye, respectively, and in addition the experimental wettability behavior of the studied materials has also been explained. It is important to note that the toxicological predictions suggested no mutagenic, tumorigenic or reproductive effects; moreover, an anti-inflammatory effect has been shown. Finally, the improvement in the cicatricial effect of the novel materials has been conveniently explained by comparing the poly-caprolactone data obtained in the experimental assessments. Full article

Aflatoxin B₁ (AFB₁) exhibits the most potent mutagenic and carcinogenic activity among aflatoxins. For this reason, AFB₁ is recognized as a human group 1 carcinogen by the International Agency of Research on Cancer. Consequently, it is essential to determine its properties and behavior in different chemical systems. The chemical properties of AFB₁ can be explored using computational chemistry, which has been employed complementarily to experimental investigations. The present review includes in silico studies (semiempirical, Hartree–Fock, DFT, molecular docking, and molecular dynamics) conducted from the first computational study in 1974 to the present (2022). This work was performed, considering the following groups: (a) molecular properties of AFB₁ (structural, energy, solvent effects, ground and the excited state, atomic charges, among others); (b) theoretical investigations of AFB₁ (degradation, quantification, reactivity, among others); (c) molecular interactions with inorganic compounds (Ag⁺, Zn²⁺, and Mg²⁺); (d) molecular interactions with environmentally compounds (clays); and (e) molecular interactions with biological compounds (DNA, enzymes, cyclodextrins, glucans, among others). Accordingly, in this work, we provide to the stakeholder the knowledge of toxicity of types of AFB₁-derivatives, the structure–activity relationships manifested by the bonds between AFB₁ and DNA or proteins, and the types of strategies that have been employed to quantify, detect, and eliminate the AFB₁ molecule. Full article

Lower activity of the histaminergic system is associated with neurological disorders, including Alzheimer’s disease (AD). Thus, the enhancement of histaminergic neurotransmission by inhibition of histamine N-methyl transferase (HNMT), which degrades histamine, appears as an important approach. For this purpose, rigid and flexible molecular docking studies of 185 FDA-approved drugs with the HNMT enzyme were carried out to select two compounds to perform molecular dynamics (MD) simulations to evaluate the binding free energies and stability of the enzyme–drug complexes. Finally, an HNMT inhibition assay was performed to corroborate their effect towards HNMT. Molecular docking studies with HNMT allowed the selection of dihydroergotamine and vilazodone since these molecules showed the lowest Gibbs free energy values. Analysis of the binding mode of vilazodone showed interactions with the binding pocket of HNMT with Glu28, Gln143, and Asn283. In contrast, dihydroergotamine binds to the HNMT active site in a different location, apparently because it is overall the more rigid ligand compared to flexible vilazodone. HNMT inhibitory activity for dihydroergotamine and vilazodone was corroborated (IC₅₀ = 72.89 μM and 45.01 μM, respectively) by in vitro assays. Drug repurposing of HNMT was achieved by employing computational studies. Full article

The coordination of one and two aflatoxin B₁ (AFB₁, a potent carcinogen) molecules with chlorophyll a (chl a) was studied at a theoretical level. Calculations were performed using the M06-2X method in conjunction with the 6-311G(d,p) basis set, in both gas and water phases. The molecular electrostatic potential map shows the chemical activity of various sites of the AFB₁ and chl a molecules. The energy difference between molecular orbitals of AFB₁ and chl a allowed for the establishment of an intermolecular interaction. A charge transfer from AFB₁ to the central cation of chl a was shown. The energies of the optimized structures for chl a show two configurations, unfolded and folded, with a difference of 15.41 kcal/mol. Chl a appeared axially coordinated to the plane (α-down or β-up) of the porphyrin moiety, either with the oxygen atom of the ketonic group, or with the oxygen atom of the lactone moiety of AFB₁. The complexes of maximum stability were chl a 1-α-E-AFB₁ and chl a 2-β-E-AFB₁, at −36.4 and −39.2 kcal/mol, respectively. Additionally, with two AFB₁ molecules were chl a 1-D-2AFB₁ and chl a 2-E-2AFB₁, at −60.0 and −64.8 kcal/mol, respectively. Finally, biosorbents containing chlorophyll could improve AFB₁ adsorption. Full article

Alzheimer’s disease (AD) represents the principal cause of dementia among the elderly. Great efforts have been established to understand the physiopathology of AD. Changes in neurotransmitter systems in patients with AD, including cholinergic, GABAergic, serotoninergic, noradrenergic, and histaminergic changes have been reported. Interestingly, changes in the histaminergic system have been related to cognitive impairment in AD patients. The principal pathological changes in the brains of AD patients, related to the histaminergic system, are neurofibrillary degeneration of the tuberomammillary nucleus, the main source of histamine in the brain, low histamine levels, and altered signaling of its receptors. The increase of histamine levels can be achieved by inhibiting its degrading enzyme, histamine N-methyltransferase (HNMT), a cytoplasmatic enzyme located in astrocytes. Thus, increasing histamine levels could be employed in AD patients as co-therapy due to their effects on cognitive functions, neuroplasticity, neuronal survival, neurogenesis, and the degradation of amyloid beta (Aβ) peptides. In this sense, the evaluation of the impact of HNMT inhibitors on animal models of AD would be interesting, consequently highlighting its relevance. Full article

There is ongoing interest in the alcohol industry to significantly reduce and/or add value to the liquid residue, vinasse, produced after the distillation and rectification of ethanol from sugar cane. Vinasse contains potassium, glycerol, and a protein component that can cause environmental issues if improperly disposed of. Currently, some industries have optimized their processes to reduce waste, and a significant proportion of vinasse is being considered for use as an additive in other industrial processes. In the manufacture of cement and asphalt, vinasse has been used in the mixtures at low concentrations, albeit with some physical and mechanical problems. This work is the first molecular approximation of the components of the sugar cane vinasse in an industrial context, and it provides atomic details of complex molecular events. In the current study, the major components of sugar cane vinasse, alone or complexed on the surface of calcium carbonate, were modeled and simulated using molecular dynamics. The results showed that the protein component, represented by the mannoprotein Mp1p, has a high affinity for forming hydrogen bonds with potassium and glycerol in the vinasse. Additionally, it provides atomic stability to the calcium carbonate surface, preserving the calcite crystalline structure in the same way potassium ions interact with the carbonate group through ion–dipole interactions to improve the cohesion of the modeled surface. On the contrary, when the glycerol molecule interacts with calcium carbonate using more than two hydrogen bonds, it triggers the breakdown of the crystalline structure of calcite expanding the ionic pair. Full article

Employing theoretical calculations with density functional theory (DFT) using the B3LYP/6-311++G(d,p) functional and basis set, the interaction of the aflatoxin B₁ (AFB₁) molecule and the functional groups present in the Pyracantha koidzumii biosorbent was investigated. Dissociation free energy and acidity equilibrium constant values were obtained theoretically both in solution (water) and gas phases. Additionally, the molecular electrostatic potential for the protonated molecules was calculated to verify the reactivity. Thus, methanol (hydroxyl group), methylammonium ion (amino group), acetate ion (carboxyl group), and acetone (carbonyl group), were used as representatives of the substrates present in the biomass; these references were considered using the corresponding protonated or unprotonated forms at a pH value of 5. The experimental infrared spectrophotometric data suggested the participation of these functional groups in the AFB₁ biosorption process, indicating that the mechanism was dominated by electrostatic interactions between the charged functional groups and the positively charged AFB₁ molecule. The theoretical determination indicated that the carboxylate ion provided the highest interaction energy with the AFB₁ molecule. Consequently, an enriched biosorbent with compounds containing carboxyl groups could improve the yield of the AFB₁ adsorption when using in vitro and in vivo trials. Full article

The structure of the ortho-, meta- and para- hybrid diindolylmethane-phenylboronic acids and their interactions were optimized with by a quantum chemical method, using density functional theory at the (DFT) level. Thus, infrared bands were assigned based on the scaled theoretical wavenumbers by correlating the respective experimental data of the molecules. In addition, the corresponding ¹H-/¹³C-/¹¹B-NMR experimental and theoretical chemical shifts were correlated. The target molecules showed a poor treatment of the OH shifts in the GIAO method due to the absence of explicit solvent effects in these calculations; therefore, they were explicitly considered with acetone molecules. Moreover, the electron density at the hydrogen bond critical point increased, generating stabilization energy, from weak to moderate or weak to strong, serving as an indicator of the strength of the hydrogen bond between the different intermolecular interactions. Finally, some properties related to the reactive behavior of the target molecules associated with their cytotoxic effects and metabolic pathways were also calculated. Full article