In Silico Study of Novel Cyclodextrin Inclusion Complexes of Polycaprolactone and Its Correlation with Skin Regeneration.

Three novel biomaterials obtained via inclusion complexes of ß-cyclodextrin, 6-deoxi-6-amino-ß-cyclodextrin and epithelial growth factor grafted to 6-deoxi-6-amino-ß-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 ß-cyclodextrin/polycaprolactone followed by the 6-amino-ß-cyclodextrin-polycaprolactone complex and finally the complex of epithelial growth factor anchored to 6-deoxy-6-amino-ß-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.

Green Approach Extraction of Perezone from the Roots of Acourtia platyphilla (A. Grey): A Comparison of Four Activating Modes and Supercritical Carbon Dioxide.

Perezone, a sesquiterpene quinone, is a very important molecule due to its pharmacological activities in addition to the fact that it is considered to be the first secondary metabolite isolated in the new world (America-Mexico, 1852). This study aims to offer a green comparative study about the extraction of the target molecule from the roots of the vegetable specimen Acourtia platyphilla (A. Grey). The study was performed comparing five different modes of extraction: supercritical CO2, electromagnetic infrared and microwave irradiations, mechanical-wave ultrasound versus typical mantle heating procedure. An exhaustive comparative-discussion of the obtained results is provided. It is worth noting that the corresponding quantifications were established using 1H NMR, correlating appropriately the integrals of the vinylic proton H-6 of perezone with the aromatic singlet of p-dinitrobenzene employed as an internal reference. It is also important to highlight that the four presented procedures are novel modes to extract perezone. Finally, a complementary study about the solubility of the target sesquiterpene quinone related to the use of supercritical CO2 is also reported.

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. The toxicological predictions suggest no mutagenic, tumorigenic or reproductive effects of the four target molecules. Complementarily, the results of a performed docking study show high scoring values and hydrogen bonding values in agreement with the cytotoxicity IC50 value ranking, i.e: indolylmenadione > indolylperezone > indolylplumbagine > indolylisoperezone. Consequently, it is possible to suggest an appropriate apoptotic pathway for each compound. Finally, potential metabolic pathways of the molecules were proposed.

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

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.

Epithelial Growth Factor-Anchored on Polycaprolactone/6-deoxy-6-amino-ß-cyclodextrin Nanofibers: In Vitro and In Vivo Evaluation.

Polycaprolactone (PCL) is a well-known FDA approved biomaterial for tissue engineering. However, its hydrophobic properties limit its use for skin wound healing which makes its functionalization necessary. In this work, we present the fabrication and evaluation of PCL nanofibers by the electrospinning technique, as well as PCL functionalized with 6-deoxy-6-amino-ß-cyclodextrin (aminated nanofibers). Afterwards, epithelial growth factor (EGF) was anchored onto hydrophilic PCL/deoxy-6-amino-ß-cyclodextrin. The characterization of the three electrospun fibers was made by means of field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR); Confocal-Raman Spectroscopy were used for elucidated the chemical structure, the hydrophilicity was determined by Contact Angle (CA). In vitro cell proliferation test was made by seeding embryonic fibroblast cell line (3T3) onto the electrospun mats and in vivo studies in a murine model were conducted to prove its effectivity as skin wound healing material. The in vitro studies showed that aminated nanofibers without and with EGF had 100 and 150% more cell proliferation of 3T3 cells against the PCL alone, respectively. In vivo results showed that skin wound healing in a murine model was accelerated by the incorporation of the EGF. In addition, the EGF had favorable effects in epidermal cell proliferation. The study demonstrates that a protein of high biological interest like EGF can be attached covalently to the surface of a synthetic material enriched with amino groups. This kind of biomaterial has a great potential for applications in skin regeneration and wound healing.

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. Alongside this, a timeline and scheme with summarized information of the history of this molecule is given including the "Códice Badiano de la Cruz, 1552, highlighting the year of its isolation culminating with information up to 2005. Subsequently, in a chronological order the most recent advances of the target molecule are included and organized in subsections covering the last 15-year period 2006-2020. Finally, recently submitted contributions from the laboratory of the authors are described. It is important to note that the details provided highlight the importance and relevance of perezone.

A Theoretical Study of the Adsorption Process of B-aflatoxins Using Pyracanthakoidzumii (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 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.

Polycaprolactone/Amino-ß-Cyclodextrin Inclusion Complex Prepared by an Electrospinning Technique.

Electrospun scaffolds of neat poly-ε-caprolactone (PCL), poly-ε-caprolactone/ß-cyclodextrin inclusion complex (PCL/ß-CD) and poly-ε-caprolactone amino derivative inclusion complex (PCL/ß-CD-NH2) were prepared by the electrospinning technique. The obtained mats were analyzed by a theoretical model using the Hartree⁻Fock method with an STO-3G basis set, and characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), differential scanning calorimetry (DSC), confocal-Raman spectroscopy, proton nuclear magnetic resonance (¹HNMR) and contact angle measure (CA). Different mixtures of solvents, such as dimethylformamide (DMF)-tetrahydrofuran (THF), dichlormethane (DCM)-dimethyl sulfoxide (DMSO) and 2,2,2-Trifluoroethanol (TFE), were tested in the fiber preparation. The results indicate that electrospun nanofibers have a pseudorotaxane structure and when it was prepared using a 2,2,2-Trifluoroethanol (TFE) as solvent, the nanofibers were electrospun well and, with the other solvents, fibers present defects such as molten fibers and bead-like defects into the fiber structure. This work provides insights into the design of PCL/ß-CD-NH2 based scaffolds that could have applications in the biomedical field.

A Theoretical Study of 8-Chloro-9-Hydroxy-Aflatoxin B1, the Conversion Product of Aflatoxin B1 by Neutral Electrolyzed Water.

Theoretical studies of 8-chloro-9-hydroxy-aflatoxin B1 (2) were carried out by Density Functional Theory (DFT). This molecule is the reaction product of the treatment of aflatoxin B1 (1) with hypochlorous acid, from neutral electrolyzed water. Determination of the structural, electronic and spectroscopic properties of the reaction product allowed its theoretical characterization. In order to elucidate the formation process of 2, two reaction pathways were evaluated-the first one considering only ionic species (Cl⁺ and OH(-)) and the second one taking into account the entire hypochlorous acid molecule (HOCl). Both pathways were studied theoretically in gas and solution phases. In the first suggested pathway, the reaction involves the addition of chlorenium ion to 1 forming a non-classic carbocation assisted by anchimeric effect of the nearest aromatic system, and then a nucleophilic attack to the intermediate by the hydroxide ion. In the second studied pathway, as a first step, the attack of the double bond from the furanic moiety of 1 to the hypochlorous acid is considered, accomplishing the same non-classical carbocation, and again in the second step, a nucleophilic attack by the hydroxide ion. In order to validate both reaction pathways, the atomic charges, the highest occupied molecular orbital and the lowest unoccupied molecular orbital were obtained for both substrate and product. The corresponding data imply that the C9 atom is the more suitable site of the substrate to interact with the hydroxide ion. It was demonstrated by theoretical calculations that a vicinal and anti chlorohydrin is produced in the terminal furan ring. Data of the studied compound indicate an important reduction in the cytotoxic and genotoxic potential of the target molecule, as demonstrated previously by our research group using different in vitro assays.