Indium(III) complexes with lapachol: cytotoxic effects against human breast tumor cells and interactions with DNA.

Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a 1,4-naphthoquinone-derived natural product that presents numerous bioactivities and was shown to have cytotoxic effects against several human tumor cells. Indium(III) complexes with a variety of ligands also exhibit antineoplastic activity. Indium(III) complexes [In(lap)Cl2].4H2O (1), [In(lap)2Cl(Et3N)] (2), [In(lap)3]·2H2O (3) [In(lap)(bipy)Cl2] bipy = 2,2'-bipyridine (4) and [In(lap)(phen)Cl2] phen = 1,10-phenanthroline (5) were obtained with 2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione (lapachol). Crystal structure determinations for (4) and (5) revealed that the indium(III) center is coordinated to two O atoms from lapachol, two N atoms from 1,10-phenanthroline or 2,2'-bipyridine, and two chloride anions, in a distorted octahedral geometry. Although both complexes (4) and (5) interacted with CT-DNA in vitro by an intercalative mode, only 5 exhibited cytotoxicity against MCF-7 and MDA-MB breast tumor cells. 1,10-phenanthroline and complex (5) presented cytotoxic effects against MCF-7 and MDA-MB cells, with complex (5) being threefold more active than 1,10-phenanthroline on MCF-7 cells. In addition, complex (5) significantly reduced the formation of MDA-MB-231 colonies in a clonogenicity assay. The foregoing results suggest that further studies on the cytotoxic effects and cellular targets of complex (5) are of utmost relevance.

Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation.

Dacarbazine (DTIC) is a widely prescribed oncolytic agent to treat advanced malignant melanomas. Nevertheless, the drug is known for exhibiting low and pH-dependent solubility, in addition to being photosensitive. These features imply the formation of the inactive photodegradation product 2-azahypoxanthine (2-AZA) during pharmaceutical manufacturing and even drug administration. We have focused on developing novel DTIC salt/cocrystal forms with enhanced solubility and dissolution behaviors to overcome or minimize this undesirable biopharmaceutical profile. By cocrystallization techniques, two salts, two cocrystals, and one salt-cocrystal have been successfully prepared through reactions with aliphatic carboxylic acids. A detailed structural study of these new multicomponent crystals was conducted using X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR and 1H NMR), and thermal (TG and DSC) analyses. Most DTIC crystal forms reported display substantial enhancements in solubility (up to 19-fold), with faster intrinsic dissolution rates (from 1.3 to 22-fold), contributing positively to reducing the photodegradation of DTIC in solution. These findings reinforce the potential of these new solid forms to enhance the limited DTIC biopharmaceutical profile.

Theoretical and X-Ray Evidence of Electrostatic Phosphonium anti and gauche Effects.

Sulphur, not phosphorus, is the only known third-row element capable of experiencing an electrostatic gauche effect with fluorine. Some six-membered rings containing an endocyclic phosphorus atom and a ß-fluorine substituent that can interconvert to axial (gauche relative to phosphorus) and equatorial positions were then analysed. While phosphines do not establish an electrostatic attraction between fluorine and phosphorus, some oxidised forms exhibit surprising stability for the sterically disfavoured axial orientation. Because the nature of this behaviour was not obvious, since an intramolecular hydrogen bond can appear, a phosphonium derivative was further studied and its axial conformation was found to be highly stable. A preference for the gauche arrangement appears even for the acyclic and sterically hindered (2-fluoroethyl)triphenylphosphonium cation. On the other hand, (ethane-1,2-diyl)bis(phosphonium) cations are exclusively in anti conformation due to an (+/+)-electrostatic repulsion between the positively charged phosphonium groups.

Full Equilibrium Picture in Aqueous Binary and Ternary Systems Involving Copper(II), 1-Methylimidazole-Containing Hydrazonic Ligands, and the 103-112 Human Prion Protein Fragment.

In this work, we describe two novel 1-methylimidazole N-acylhydyrazonic ligands and their interaction with copper(II) in solution. Binary systems constituted by each of these hydrazones and the metal ion were studied by potentiometric titrations. The magnitude of their affinities for zinc(II) was also determined for the sake of comparison. Additionally, a full evaluation of the copper(II) chelation profile of the new ligands in ternary systems containing a human prion protein fragment was performed. Mixed ligand complexes comprising the HuPrP103-112 fragment, copper(II) ions, and an N-acylhydrazone were characterized by potentiometry, ultraviolet-visible spectroscopy, and circular dichroism. Some of these species were also identified by electrospray ionization mass spectrometry and unequivocally assigned through their isotopic distribution pattern. To the best of our knowledge, this is the first report concerning the stability of ternary complexes involving a hydrazonic metal-protein interaction modulator, copper, and a peptide. The ability of N-acylhydrazones to prevent peptide oxidation was also examined. Both ligands can partially prevent the formation of the doubly oxidized product, a process mediated by copper(II) ions. Oxidative stress is considered an important hallmark of neurodegenerative diseases such as prion-related spongiform encephalopathies. In this context, active intervention with respect to the deleterious copper-catalyzed methionine oxidation could represent an interesting therapeutic approach.

Modified pyrazole platinum(II) complex can circumvent albumin and glutathione: Synthesis, structure and cytotoxic activity.

The synthesis and structural characterization of novel platinum complexes ([PtII(Pz)2Cl2] - C1, C2 and C3) featuring diphenyl-pyrazole derived ligands: para-fluorophenyl and para-substituted phenyl (CH3, F and Cl for L1, L2 and L3, respectively) were reported and it was also evaluated their potential antitumor activity. The elemental, molar conductivity and thermogravimetric analysis combined with FTIR, UV-vis, NMR and mass spectrometry are in agreement with the chemical structure indicated by single-crystal X-ray diffraction. The antiproliferative activities were assessed against tumor (B16F10 and 4T1) and non-tumor (BHK21) cell lines, and the cytotoxicity of the compounds was strongly increased after metal complexation displaying promising activity. It was also assessed the ability of extracellular bovine serum albumin (BSA) and glutathione (GSH) to decrease the cytotoxicity of the complexes against B16F10. It was highlighted that only the C3 activity was not disturbed in those conditions, being confirmed by flow cytometry using Anexin-V/PI to evaluate interferences in the apoptosis process, even it was not predicted by molecular docking simulations. The interaction of the synthesized compounds with calf-thymus DNA (ctDNA) and bovine serum albumin (BSA) was also investigated through spectrophotometric assays and molecular docking simulations, indicating that C1 and C2 presented better interaction with the biomacromolecules than the corresponding ligands. In addition, agarose gel electrophoresis with plasmid DNA revealed that C1-C3 are capable of interaction with DNA and modify its electrophoretic mobility.

Mono and dinuclear platinum and palladium complexes containing adamantane-azole ligands: DNA and BSA interaction and cytotoxicity.

Synthesis of dinuclear oxadiazole-adamantane platinum(II) and palladium(II) complexes (PtO, PdO) and mononuclear thiazolidine derivative complexes (PtT, PdT) was described. Characterization was performed by elemental analysis, infrared, UV-visible, 1H, 13C, 195Pt NMR spectra, MS spectroscopy and single crystal X-ray diffraction. The cytotoxicity by MTT assay against tumor and normal cell lines with or without extracellular GSH was also investigated. In general, mononuclear complexes containing thiazolidine-adamantane ligands were more cytotoxic than oxadiazole-adamantane derivatives. PtT complex proved to be as active as cisplatin. Dinuclear compounds were considered inactive to cells in evaluated conditions, due to their high stability with ligands in a chelated and bridged way. Results suggest that GSH cannot be considered a target. DNA- and BSA-binding interactions were evaluated using UV-visible and fluorescence spectroscopy, intercalating dyes and molecular docking. Upon coordination to platinum(II), the cytotoxic effect was appreciably improved against tested cell lines, in comparison to free thiazolidine ligand. Comparing thiazolidine derivatives, it is noticeable that the less active compound (PdT) presents stronger interaction with BSA, while PtT has the weaker interaction with BSA and relatively strong binding to isolated DNA, resulting in the most cytotoxic complex. This work shows that the presence of metal is significant but it should be available for interaction. The high lability of palladium complex made this stay retainable in BSA and two metal atoms do not increase activity if it is not able to do any interaction.

Binucleating Hydrazonic Ligands and Their µ-Hydroxodicopper(II) Complexes as Promising Structural Motifs for Enhanced Antitumor Activity.

Very few inorganic antineoplastic drugs have entered the clinic in the last decades, mainly because of toxicity issues. Because copper is an essential trace element of ubiquitous occurrence, decreased side effects could be expected in comparison with the widely used platinum anticancer compounds. In the present work, two novel hydrazonic binucleating ligands and their µ-hydroxo dicopper(II) complexes were prepared and fully characterized. They differ by the nature of the aromatic group present in their aroylhydrazone moieties: while H3L1 and its complex, 1, possess a thiophene ring, H3L2 and 2 contain the more polar furan heterocycle. X-ray diffraction indicates that both coordination compounds are very similar in structural terms and generate dimeric arrangements in the solid state. Positive-ion electrospray ionization mass spectrometry analyses confirmed that the main species present in a 10% dimethyl sulfoxide (DMSO)/water solution should be [Cu2(HL)(OH)]+ and the DMSO-substituted derivative [Cu2(L)(DMSO)]+. Scattering techniques [dynamic light scattering (DLS) and small-angle X-ray scattering] suggest that the complexes and their free ligands interact with bovine serum albumin (BSA) in a reversible manner. The binding constants to BSA were determined for the complexes through fluorescence spectroscopy. Moreover, to gain insight into the mechanism of action of the compounds, calf thymus DNA binding studies by UV-visible and DLS measurements using plasmid pBR322 DNA were also performed. For the complexes, DLS data seem to point to the occurrence of DNA cleavage to Form III (linear). Both ligands and their dicopper(II) complexes display potent antiproliferative activity in a panel of four cancer cell lines, occasionally even in the submicromolar range, with the complexes being more potent than the free ligands. Our data on cellular models correlate quite well with the DNA interaction experiments. The results presented herein show that aroylhydrazone-derived binucleating ligands, as well as their dinuclear µ-hydroxodicopper(II) complexes, may represent a promising structural starting point for the development of a new generation of highly active potential antitumor agents.

Dietary supplements and fatigue in patients with breast cancer: a systematic review.

PURPOSE: Cancer-related fatigue (CRF) is defined as a distressing, persistent, and subjective sense of physical or emotional and/or cognitive exhaustion. The treatment of CRF includes pharmacological and non-pharmacological therapies; dietary strategies with promising results have also been used. This study aimed to identify dietary supplements that improve fatigue in patients with breast cancer. METHODS: A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data were obtained from PubMed, Scopus, MEDLINE, CENTRAL, and CINAHL databases using the following MeSH terms: breast neoplasms, dietary supplements, diet, and fatigue. In addition, the Google and Google Scholar search engines were used to find grey literature. Methodological quality was evaluated using the risk of bias in randomised clinical trials in the systematic Cochrane reviews, and the quality of the evidence was also analysed using the GRADE system. RESULTS: A total of 893 studies were assessed, of which eight were included in the review, with 932 women diagnosed with breast cancer. The most commonly used supplements that improve fatigue were guarana, acetyl-L-carnitine, and co-enzyme Q10. Two studies had a low risk of bias in all categories and three had high-quality evidence. CONCLUSIONS: Dietary supplements or diet patterns are seldom used to treat fatigue in patients with breast cancer. The results of this review showed that guarana extract and a diet rich in whole foods, omega-3 fatty acids, fruits, and vegetables could be used to treat CRF in patients with breast cancer. The studies had a low risk of bias with high-quality evidence on the efficacy of the interventions in treating fatigue in the study population.

Effect of exercise on pain and functional capacity in breast cancer patients.

PURPOSE: To assess the influence of combined training on pain, fatigue, maximal oxygen uptake (VO2 max), body mass index (BMI), flexibility, and strength in patients with breast cancer. METHODS: A controlled pilot study with 28 patients undergoing chemotherapy, radiation therapy, and clinical observation in a renowned cancer treatment center; the patients were aged from 30 to 59 years old and were not engaged in physical training for three months previously. The Study Group (SG) underwent 12 weeks of training, including three 60-min sessions of aerobic exercise and resistance training, and two sessions of flexibility training per week; each flexibility exercise lasted 20 s and was performed in sets of three repetitions. The Control Group (CG) received only the standard hospital treatment. Participants were evaluated at the beginning of the study to establish a baseline and reevaluated at the end of 12 weeks. RESULTS: Patients in the SG showed a significant decrease in total pain points (p = 0.0047), pain intensity (p = 0.0082), and the extent to which pain interfered with their daily life (p = 0.0047). There was an increase in maximum oxygen uptake (p = 0.0001), flexibility (p = 0.0001), and strength on both sides (right p = 0.0001 and left p = 0.0008). No significant differences were observed in fatigue (p = 0.0953) or BMI (p = 0.6088). CONCLUSION: Combined training was effective in decreasing pain and increasing VO2 max, flexibility and static strength in patients with breast cancer. TRIAL REGISTRATION: NCT03061773 . Registered on February 19, 2017, 'retrospectively registered'.

Chiral brønsted Acid-catalyzed stereoselective Mannich-type reaction of azlactones with aldimines.

A highly diastereo- and enantioselective Mannich-type reaction of azlactones with aldimines catalyzed by a chiral phosphoric acid is described. Only 3 mol % catalyst was required to prepare the Mannich adducts in good yields with high stereochemical control (up to >19:1 dr, >99:1 er). Moreover, the final product contains two consecutive stereogenic centers, one of which is quaternary.

Experimental and theoretical structural investigation of an ionic Nd coordination polymer.

Research concerning coordination polymers has been intense due to their significant variability and structural stability. With this in mind, an ionic neodymium coordination polymer was synthesized, composed of an anionic one-dimensional polymer interconnected to a cationic three-dimensional porous polymer, poly[dodecaaquabis(µ-pyridine-4-carbohydrazide-κ2N:O)bis(µ2-4-sulfobenzoato-κ2O:O')bis(µ3-4-sulfobenzoato-κ3O:O':O'')trineodymium(III)] catena-poly[aquabis(µ-pyridine-4-carbohydrazide-κ2N:O)bis(µ2-4-sulfobenzoato-κ2O:O')neodymium(III)] 4.33-hydrate, {[Nd3(C7H4O5S)4(C6H7N3O)2(H2O)12][Nd(C7H4O5S)2(C6H7N3O)2(H2O)]·4.33H2O}n. The ligands used were 4-sulfobenzoate (PSB) and pyridine-4-carbohydrazide, popularly known as isoniazid (INH), an antibiotic drug. The compound crystallizes in the monoclinic space group C2/c, with Z = 4. Solid-state calculations suggest that the crystal structure is mainly stabilized by hydrogen bonds, i.e. O-H...O and N-H...O interactions among the polymers, and by van der Waals interactions involving the organic side chains. This net is tetragonal, 2-nodal 3,4-connected, and can be described as the dmd (sqc 528) type.

Distributed functional-group polarizabilities in polypeptides and peptide clusters toward accurate prediction of electro-optical properties of biomacromolecules.

CONTEXT: Aiming at accurately predicting electro-optical properties of biomolecules, this work presents distributed atomic and functional-group polarizability tensors for a series of polypeptides and peptide clusters constructed from glycine and its residuals. By partitioning the electron density using the quantum theory of atoms in molecules, we demonstrated a very good transferability of the group polarizabilities. We were able to identify and extract the most efficient functional groups capable of generating the largest electrical susceptibility in condensed phases. Both the isotropic polarizability and its anisotropy were used to understand the way functional groups act as sources of linear optical responses, how they interact with each other reinforcing the macroscopic optical behavior within the material, and how covalent bonds and non-covalent interactions, such as hydrogen bonds, determine refractive indices and birefringence. Particular attention is devoted to the peptide bonds as they provide links to build biomacromolecules or polymers. An adequate quantum-mechanical treatment of at least the first interaction sphere of a given functional group is required to properly describe the effects of mutual polarization, but we identified optimum cluster size and shape to better estimate polarizabilities and dipole moments of larger molecules or molecular aggregates from the knowledge of the electron density of a central molecule or amino acid residual that is representative of the bulk. The strategy outlined here is a fast yet effective tool for estimating the optical properties of proteins but could eventually find application in the rational design of optical organic materials as well. METHODS: Electronic-structure calculations were performed on the Gaussin16 program at the DFT level using the CAMB3LYP functional and the double-ζ quality Dunning basis set aug-cc-pVDZ. Electron density partitioning followed the concepts of the Quantum Theory of Atoms and Molecules (QTAIM) and was performed using the AIMAll program. The locally developed Polaber routine was applied to calculate dipole moment vectors and polarizability tensors. It was amended to include the effects of the local field on a given central molecule by means of a modified Atom-Dipole Interaction Model (ADIM).

New mescaline-related N-acylhydrazone and its unsubstituted benzoyl derivative: Promising metallophores for copper-associated deleterious effects relief in Alzheimer's disease.

Alzheimer's disease (AD) is related to the presence of extracellular aggregated amyloid-ß peptide (Aß), which binds copper(II) with high affinity in its N-terminal region. In this sense, two new 1-methylimidazole-containing N-acylhydrazonic metallophores, namely, X1TMP and X1Benz, were synthesized as hydrochlorides and characterized. The compound X1TMP contains the 3,4,5-trimethoxybenzoyl moiety present in the structure of mescaline, a natural hallucinogenic protoalkaloid that occurs in some species of cacti. Single crystals of X1Benz, the unsubstituted derivative of X1TMP, were obtained. The experimental partition coefficients of both compounds were determined, as well as their apparent affinity for Cu2+ in aqueous solution. Ascorbate consumption assays showed that these N-acylhydrazones are able to lessen the production of ROS by the Cu(Aß)-system, and a short-time scale aggregation study, measured through turbidity and confirmed by TEM images, revealed their capacity in preventing Aß fibrillation at equimolar conditions in the presence and absence of copper. 1H15N HSQC NMR experiments demonstrated a direct interaction between Aß and X1Benz, the most soluble of the compounds. The Cu2+ sequestering potential of this hydrazone towards Aß was explored by 1H NMR. Although increasing amounts of X1Benz were unexpectedly not efficient at removing the metal-induced perturbations in Aß backbone amides, the broadening effects observed on the compound's signals indicate the formation of a ternary Aß­copper-X1Benz species, which can be responsible for the observed ROS-lessening and aggregation-preventing activities. Overall, the N-acylhydrazones X1TMP and X1Benz have shown promising prospects as agents for the treatment of AD.

Copper(II) complexes of a furan-containing aroylhydrazonic ligand: syntheses, structural studies, solution chemistry and interaction with HSA.

Copper(II) complexes have become a potential alternative to the use of platinum drugs in cancer therapy due to their multi-target mode of action. In this context, we report the syntheses of new mononuclear and dinuclear coordination compounds of this element, 1 and 2, derived from the ligand 5-methylsalicylaldehyde 2-furoyl hydrazone (H2L). All three compounds were structurally and spectroscopically characterized, both in the solid state and in solution. In 1, Cu is coordinated by three donor-atoms from the hydrazonic ligand and one chloride ion. H2L is deprotonated at the phenol oxygen. The dinuclear complex 2 is, on the other hand, a dimeric form of 1 in which the chloride ions of a pair of mononuclear units are lost and phenoxo bridges take their places, double-connecting the metal centres and resulting in a single species with the ligand fully deprotonated. The compounds were fairly stable in aqueous medium at room temperature. An experimental-theoretical combined approach demonstrated that all of them are able to bind human serum albumin (HSA), although at different sites and with diverse stoichiometries and affinities (as concluded by the calculated binding energies). In view of this, and due to the well-known antiproliferative activity of hydrazone-containing copper complexes, we consider the compounds presented in here promising, and believe that they deserve more profound studies regarding the assessment of their potential against tumour cell lines.

Memantine-Derived Schiff Bases as Transdermal Prodrug Candidates.

Condensation reactions of salicylaldehyde, 2-pyridinecarboxaldehyde, and pyridoxaldehyde with memantine (Me) produced novel memantine-derived Schiff bases (1-3). Speciation predictions and calculations of Log P, Log D, and of the percentage (%) of neutral species for (1-3) were carried out. In comparison with Me, the Schiff bases presented increased log P and log D in all cases and pH values, suggesting higher hydrophobicity. The determined solubilities in n-octanol were 34.7 mg/mL for memantine hydrochloride and 67.3 mg/mL for (3). According to the molecular weights and calculated logP, compounds (1-3) are suitable for transdermal administration, especially compound (3). In addition, hydrolysis of 3 with the release of pyridoxal, a daily cofactor in human metabolism, was observed. The results suggested that 3 is the most promising compound and that formation of the pyridoxal Schiff base with Me might be an effective strategy to obtain a prodrug candidate with increased lipophilicity, which would be able to passively cross biological barriers during transdermal delivery and might have applications in the treatment of Alzheimer's disease and other neurological disorders.

cis-Dichloridobis-(5,5'-dimethyl-2,2'-bipyridine)-manganese(II) 2.5-hydrate.

The metal site in the title compound [MnCl(2)(C(12)H(12)N(2))(2)]·2.5H(2)O has a distorted octa-hedral geometry, coordinated by four N atoms of two 5,5'-dimethyl-2,2'-dipyridine ligands and two Cl atoms. Two and a half water molecules of hydration per complex unit are observed in the crystal structure. The compounds extend along the c axis with O-H⋯Cl, O-H⋯O, C-H⋯Cl and C-H⋯O hydrogen bonds and π-π inter-actions [centroid-centroid distance = 3.70 (2) Å] contributing substanti-ally to the crystal packing. The Mn and one of the water O atoms, the latter being half-occupied, are located on special positions, in this case a rotation axis of order 2.

Ethyl 2-[(carbamoyl-amino)-imino]-propano-ate hemihydrate.

The title compound, C(6)H(11)N(3)O(3)·0.5H(2)O, has two independent mol-ecules and one mol-ecule of water in the asymmetric unit. The crystal packing is stabilized by inter-molecular N-H⋯N, O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds. These inter-actions form a two-dimensional array in the ab plane with a zigzag motif which has an angle close to 35° between the zigzag planes. The hydrogen bonding can be best described using the graph-set notation as N(1) = C(10)R(2) (2)(10)R(2) (2)(8) and N(2) = R(6) (4)(20)R(2) (2)(8).

Ethyl 2-[(carbamothioyl-amino)-imino]-propano-ate.

The title compound, C(6)H(11)N(3)O(2)S, consists of a roughly planar mol-ecule (r.m.s deviation from planarity = 0.077 Šfor the non-H atoms) and has the S atom in an anti position to the imine N atom. This N atom is the acceptor of a strongly bent inter-nal N-H⋯N hydrogen bond donated by the amino group. In the crystal, mol-ecules are arranged in undulating layers parallel to (010). The mol-ecules are linked via inter-molecular amino-carboxyl N-H⋯O hydrogen bonds, forming chains parallel to [001]. The chains are cross-linked by N(carbazone)-H⋯S and C-H⋯S inter-actions, forming infinite sheets.

Theoretical and experimental spectroscopic investigation of new Eu(III)-FOD complex containing 2-pyrrolidone ligand.

The preparation and photoluminescent properties of the new [Eu(FOD)3(2-Pyr)2] complex (FOD = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octadionate; 2-Pyr = 2-pyrrolidone) are reported. The obtained complex was characterized by elemental analysis, complexometric titration using EDTA, infrared spectroscopy, and single-crystal X-ray diffraction studies. The coordination polyhedron of the complex is described as a distorted square antiprismatic with both 2-Pyr monodentate ligands coordinated to Eu(III) via the oxygen atoms, in neutral form, while the three FOD molecules are coordinated in the anionic form. Structural modeling at the PBE1PBE/SVP/MWB52 level of theory provided a geometry in excellent agreement with the one obtained experimentally. Spectroscopy properties such as intensity parameters (Ω2 and Ω4), radiative emission rate (Arad), and chemical partition of Arad for [Eu(FOD)3(2-Pyr)2] and [Eu(FOD)3(H2O)2] were calculated by using the QDC model with help of the semiempirical wavefunctions. The modeling of the ligand-to-metal energy transfer for both complexes was performed, allowing to obtain the theoretical emission quantum yield and to characterize the most relevant molecular orbitals involved.

Evidence of the validity of the Food and Nutritional Security Scale for adolescents (ESANa). / Evidências de validade da Escala de Segurança Alimentar e Nutricional para adolescentes (ESANa).

This study aimed to develop a valid and reliable scale for assessing food and nutritional insecurity, specifically in adolescents. The initial version of the scale consisted of two subscales: perception of food insecurity and perception of nutritional security. The items were submitted to content analysis (n = 4) by a group of food and nutrition security experts, and semantic analysis (n = 20) by a group of adolescents conveniently sampled from the target population. After adjustments, the final version of the scale was applied to adolescent students (n = 425) aged 12 to 18 years (m = 14.32±0.96; CV = 6.7%). A two-factor model was the most appropriate after performing exploratory factor analysis. The subscales showed modest values of the alpha coefficient (0.69 and 0.60, respectively). Daily consumption of fruits, vegetables and soft drinks was significantly associated with higher scores in the food and nutrition security perception scale. Therefore, it is recommended to combine food access-based items with other aspects related to attitudes and behaviors towards healthy eating in order to achieve a more accurate picture of adolescent's needs and better guide public policies.

O objetivo do trabalho foi desenvolver uma escala válida e fidedigna para a avaliação de insegurança alimentar e nutricional especificamente em adolescentes. A versão inicial da escala foi composta por duas subescalas: percepção de insegurança alimentar e percepção de segurança nutricional. Os itens elaborados foram submetidos à análise de conteúdo por peritos em segurança alimentar e nutricional (n = 4) e à análise semântica por adolescentes selecionados por conveniência e oriundos da população alvo (n=20). Após ajustes, a versão final da escala foi aplicada junto a adolescentes escolares (n = 425) com idade entre 12 e 18 anos (m = 14,32±0,96; CV = 6,7%). Após realização de análise fatorial exploratória, um modelo de dois fatores foi o que se mostrou mais adequado. As subescalas avaliadas apresentaram valores modestos do coeficiente alfa (0,69 e 0,60, respectivamente). Consumo diário de frutas, verduras e refrigerantes se mostrou significativamente associado a escores mais elevados na escala de percepção de segurança alimentar e nutricional. Sugere-se a viabilidade de combinar itens com base no acesso a alimentos com outros relacionados a atitudes e práticas de alimentação saudável de modo a obter um retrato mais aproximado das necessidades dos adolescentes e melhor orientar políticas públicas.