Dihydroergotamine Increases Histamine Brain Levels and Improves Memory in a Scopolamine-Induced Amnesia Model.

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).

Analysing the effect caused by increasing the molecular volume in M1-AChR receptor agonists and antagonists: a structural and computational study.

M1 muscarinic acetylcholine receptor (M1-AChR), a member of the G protein-coupled receptors (GPCR) family, plays a crucial role in learning and memory, making it an important drug target for Alzheimer's disease (AD) and schizophrenia. M1-AChR activation and deactivation have shown modifying effects in AD and PD preclinical models, respectively. However, understanding the pharmacology associated with M1-AChR activation or deactivation is complex, because of the low selectivity among muscarinic subtypes, hampering their therapeutic applications.

Design of Two New Sulfur Derivatives of Perezone: In Silico Study Simulation Targeting PARP-1 and In Vitro Study Validation Using Cancer Cell Lines.

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 (-) 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.

Synthesis, Cytotoxic Activity and In Silico Study of Novel Dihydropyridine Carboxylic Acids Derivatives.

To aid the possible prevention of multidrug resistance in tumors and cause lower toxicity, a set of sixteen novel dihydropyridine carboxylic acids derivatives were produced; thus, the activation of various ynones with triflic anhydride was performed, involving a nucleophilic addition of several (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 (, and ) were selected to perform in silico studies due to the highest cytotoxic activity towards the HCT-15 cell line (7.

Computational Studies of Aflatoxin B (AFB): A Review.

Aflatoxin B (AFB) exhibits the most potent mutagenic and carcinogenic activity among aflatoxins. For this reason, AFB 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.

Drug Repurposing to Inhibit Histamine -Methyl Transferase.

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 -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.

The Ability of Chlorophyll to Trap Carcinogen Aflatoxin B: A Theoretical Approach.

The coordination of one and two aflatoxin B (AFB, a potent carcinogen) molecules with chlorophyll 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 AFB and molecules.

A Timeline of Perezone, the First Isolated Secondary Metabolite in the New World, Covering the Period from 1852 to 2020.

This chapter covers a sesquiterpene quinone, commonly named perezone. This molecule is documented as the first secondary metabolite isolated in crystalline form in the New World in 1852. An introduction, with its structure, the IUPAC nomenclature, and the most recent physical and spectroscopic characterizations are firstly described initially.

Inhibition of Astrocytic Histamine -Methyltransferase as a Possible Target for the Treatment of Alzheimer's Disease.

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.

Validation by Molecular Dynamics of the Major Components of Sugarcane Vinasse, On a Surface of Calcium Carbonate (Calcite).

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.

Phenomenological study of the synthesis of pure anhydrous β-lactose in alcoholic solution.

Lactose is an important additive because of its food, pharmaceutical, and cosmetic applications. Among lactose polymorphs, anhydrous β-lactose stands out due to its thermodynamic stability. Thus, a simple method to produce the inter-conversion from monohydrate α-lactose to anhydrous β-lactose was investigated employing a methanolic solution and different reaction variables (catalyst type, temperature, and stirring).

A Theoretical Study of the Adsorption Process of B-aflatoxins Using (Hayata) Rehder Biomasses.

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 B (AFB) molecule and the functional groups present in the 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.

In vitro and computational studies of natural products related to perezone as anti-neoplastic agents.

Many natural phyto-products as perezone (Per) exhibit anti-cancer activities. Using experimental and computational studies, it was described that Poly ADP-ribose polymerase 1(PARP-1) inhibition and the induction of oxidative stress state explain the pro-apoptotic activity of Per. The aim of this study was to evaluate two phyto-products related to Per as anti-cancer agents: hydroxyperezone (OHPer) and its monoangelate (OHPer-MAng).

In vitro and computational studies showed that perezone inhibits PARP-1 and induces changes in the redox state of K562 cells.

Cancer is one of the leading causes of morbidity and mortality worldwide. This disease is characterized by uncontrolled growth and proliferation of abnormal cells with a high probability to develop metastasis. Recently, it was demonstrated that perezone, a sesquiterpene quinone, is capable to induce cell death in leukemia (K562), prostate (PC-3), colorectal (HCT-15) and lung (SKLU-1) cancer cell lines; however, its mechanism of action is unknown.

Reinvestigation of Acetophenones Oxidation by Performic Acid in Formic Acid.

The Baeyer-Villiger (BV) reaction of acetophenones R-COCH (R = phenyl, 4-methylphenyl, 3,4-dimethoxyphenyl) with performic acid (PFA) in formic acid (FA) as the catalyst and solvent was reinvestigated using the MPWB1K functional in conjunction with the 6-311G(d,p) and 6-311++G(d,p) basis sets. For the acid-catalyzed addition step, we used the eight-membered ring transition structure proposed in our previous work. The calculated and experimental results obtained for the BV reaction under the mentioned conditions lead to the conclusion that our mechanism is more reliable than the one reported by Liu and co-workers, in which the acid-catalyzed first step involves a transition state with a six-membered ring structure.

A DFT Study of the Geometrical, Spectroscopical and Reactivity Properties of Diindolylmethane-Phenylboronic Acid Hybrids.

The structure of the -, - and - 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-/C-/B-NMR experimental and theoretical chemical shifts were correlated.

In silico Study of the Pharmacologic Properties and Cytotoxicity Pathways in Cancer Cells of Various Indolylquinone Analogues of Perezone.

Several indolylquinone analogues of perezone, a natural sesquiterpene quinone, were characterized in this work by theoretical methods. In addition, some physicochemical, toxicological and metabolic properties were predicted using bioinformatics software. The predicted physicochemical properties are in agreement with the solubility and cLogP values, the penetration across the cell membrane, and absorption values, as well as with a possible apoptosis-activated mechanism of cytotoxic action.

Virtual and In Vitro Screens Reveal a Potential Pharmacophore that Avoids the Fibrillization of Aβ1-42.

Among the multiple factors that induce Alzheimer's disease, aggregation of the amyloid β peptide (Aβ) is considered the most important due to the ability of the 42-amino acid Aβ peptides (Aβ1-42) to form oligomers and fibrils, which constitute Aβ pathological aggregates. For this reason, the development of inhibitors of Aβ1-42 pathological aggregation represents a field of research interest. Several Aβ1-42 fibrillization inhibitors possess tertiary amine and aromatic moieties.