Publications

Abstract Emerging threats to human health require a concerted effort to search for new treatment therapies. One of the biggest challenges is finding medicines with few or no side effects. Natural products have historically contributed to major advances in the field of pharmacotherapy, as they offer special characteristics compared to conventional synthetic molecules. Interest in natural products is being revitalized, in a continuous search for lead structures that can be used as models for the development of new medicines by the pharmaceutical industry. Chromone and chromanones are recognized as privileged structures and useful templates for the design of diversified therapeutic molecules with potential pharmacological interest. Chromones and chromanones are widely distributed in plants and fungi, and significant biological activities, namely antioxidant, anti-inflammatory, antimicrobial, antiviral, etc., have been reported for these compounds, suggesting their potential as lead drug candidates. This review aims to update the literature published over the last 6 years (2018-2023) regarding the natural occurrence and biological activity of chromones and chromanones, highlighting the recent findings and the perspectives that they hold for future research and applications namely in health, cosmetic, and food industries.

Abstract The excessive use of biocides has considerable environmental and economic impacts; this is why new technologies have been sought to decrease the concentration levels applied in an effort to reduce the use of these substances. Microencapsulation using cyclodextrins has been widely used in the food and pharmaceutical industries as a way of reducing the concentrations of the active substance necessary to achieve a biological effect and/or eliminate its irritating or toxicological effects. In this study, the inclusion complexation behavior and binding ability of benzothiazolinone (BIT) with different beta-cyclodextrins (beta-CD, HP-beta-CD, and Me-beta-CD) was investigated. The intermolecular interactions were examined through UV and FTIR spectroscopy, DSC, 1D 1H NMR, and 2D ROESY. The highest stability constant was observed for the BIT/Me-beta-CD inclusion complex (299.5 +/- 2.9 M-1). Antibacterial activity was investigated against Staphylococcus aureus and Escherichia coli, and the results revealed that the BIT/Me-beta-CD inclusion complex displays a higher antibacterial activity than BIT. The acute toxicity of the biocide and inclusion complex was also examined using the photobacterium Aliivibrio fischeri. Although BIT exhibited higher toxicity than the inclusion complex, further investigation is needed due to the quorum quenching effect of beta-CDs. The data found suggest that BIT microencapsulation can increase its aqueous solubility and can be used as an effective tool to improve its chemical, biological, and ecotoxicological properties.

Abstract Adherence to topical treatments is low and is known to be influenced by the vehicle properties. Betamethasone dipropionate (BD) is an anti-inflammatory steroid, used in psoriasis treatment in the form of an ointment, cream, or solution. The aim of this work was to develop a new vehicle for BD, focusing on the preferences of patients with psoriasis as a strategy to improve treatment adherence. Two vehicles with an aqueous external phase were explored: an emulgel and a hydrogel based on a cyclodextrin inclusion complex used to improve the aqueous solubility of BD. Since BD solubilization was not fully achieved in the hydrogel, only the emulgel was selected for further characterization. This new vehicle (emulgel) is characterized by its white, shiny appearance and good spreading properties. In comparison with petrolatum, a lower residue, higher evaporation rate, lower stickiness, and reduced ability to stain polyester fabric were observed. This vehicle also showed shear thinning behavior. The impact of this new vehicle on adherence to topical treatments should be further confirmed in clinical settings.

Abstract The emergence of a large number of new psychoactive substance (NPS) on the global drug market poses a significant risk to public health and a challenge to drug control systems. Over the last decades, electrochemical sensing of illicit drugs has experienced a very significant growth, since these techniques can provide fast, portable, sensitive and low-cost detection alternatives for the analysis of drugs, metabolites and/or transformation products in different matrices. To understand and clarify the oxidative mechanism of piperazine designer drugs, the voltammetric profile of psychoactive piperazine derivatives 1-phenylpiperazine (PhPIP), 3-chlorophenylpiperazine (mCPP), 3-trifluoromethylphenylpiperazine (TFMPP), 4-fluorophenylpiperazine (pFPP) and benzylpiperazine (BZP) has been investigated at a glassy carbon electrode. The data found showed the crucial role of the aromatic amine, present in PhPIP, mCPP, pFPP and TFMPP molecular' structures, on the oxidative profiles. The voltammetric behavior of BZP is quite different from those found for the other piperazines under study due to the nature of the amine group present in BZP molecular' structure, benzylic instead of an aromatic amine. This work can be a helpful contribution to the ability to predict and identify metabolites and the development of new analytical approaches that can allow the rapid and specific quantitative detection of psychoactive piperazine derivatives.

Abstract The importance of isothiazole and of compounds containing the isothiazole nucleus has been growing over the last few years. Isothiazolinones are used in cosmetic and as chemical additives for occupational and industrial usage due to their bacteriostatic and fungiostatic activity. Despite their effectiveness as biocides, isothiazolinones are strong sensitizers, producing skin irritations and allergies and may pose ecotoxicological hazards. Therefore, their use is restricted by EU legislation. Considering the relevance and importance of isothiazolinone biocides, the present review describes the state-of-the-art knowledge regarding their synthesis, antibacterial components, toxicity (including structure-activity-toxicity relationships) outlines, and (photo)chemical stability. Due to the increasing prevalence and impact of isothiazolinones in consumer's health, analytical methods for the identification and determination of this type of biocides were also discussed.

Abstract Caffeic acid phenethyl ester (CAPE) is a bioactive polyphenolic compound obtained from propolis extract. Although it has a broad therapeutic potential, the bioavailability of CAPE is limited, due to reduced solubility and poor plasmatic stability. Efforts to reduce these pharmacokinetic drawbacks resulted in the synthesis of caffeic acid phenethyl amide (CAPA). Cyclodextrins have been proved as promising excipients for the formulation of active ingredients. Herein, we report the inclusion complexation behavior and binding ability of CAPE and CAPA with hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The supramolecular interactions were examined through UV and FTIR spectroscopy, DSC, H-1 NMR and 2D ROESY. The CAPE/HP-beta-CD and CAPA/HP-beta-CD inclusion complexes stability constants were determined to be, respectively, 2911.6 and 584.6 M-1 in water and 2866.2 and 700.1 M-1 at physiological pH. The aqueous solubility increased notably, proving that HP-beta-CD can be potentially useful to improve the biological, chemical and physical properties of CAPE and CAPA.

Abstract A simple and expedite electrochemical methodology was developed for the determination of ciprofloxacin, based on a glassy carbon (GC) electrode modified by a combination of multi-walled carbon nanotubes (MWCNT) with -cyclodextrin (-CD) incorporated in a polyaniline film. The combined use of -CD and MWCNT in the electrochemical sensor leads to a significant signal improvement. The -CD/MWCNT modified GC electrode exhibited efficient electrocatalytic behavior in the oxidation of ciprofloxacin with relatively high sensitivity, stability and lifetime. Molecular modeling studies showed that ciprofloxacin binds preferably to -CD rather than to CNT edges, leading to an improved sensitivity of the sensor. Under optimized conditions, a linear calibration curve was obtained for ciprofloxacin in the concentration range 10-80 mu M with a detection limit of 50nM. The analytical performance of this sensor was evaluated for the detection of ciprofloxacin in a wastewater treatment plant effluent.

Abstract The herbicide terbuthylazine (TBA) is widely used for preemergence or postemergence control of many grass and broadleaf weeds and has, besides other issues, a poor aqueous solubility profile that results in reduced bioavailability. Cyclodextrins and modified cyclodextrins were considered, among other substances, appropriate agents for improving pesticide water solubility. Therefore, the inclusion complex formation of terbuthylazine with beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was studied to attain its aqueous solubility enhancement. Their characterization was accomplished with different analytical techniques, namely, by UV-Vis, DSC, FTIR, and 1 HNMR. From the analysis of the complexation performance of the herbicide it was concluded that the interaction of terbuthylazine with CDs leads to the formation of inclusion complexes with a stoichiometry of 1 : 1. The association constants of the TBA/beta-CD and TBA/HP-beta-CD complexes were determined by UV. The mean values obtained for the stability constants are 460.4 +/- 26.5 and 532.1 +/- 27.6 to TBA/beta-CD and TBA/HP-beta-CD, respectively. H-1 NMR data corroborate the formation of the TBA/beta-CD and TBA/HP-beta-CD complexes synthesized by the kneading method. A formulation incorporating TBA cyclodextrin complexes might lead to an improvement in terbuthylazine bioavailability. The development of TBA-CD formulations may be interesting since it would enable, through their inclusion into the hydrophobic cavity of CDs, enhancement of solubility, bioavailability, and stability of the herbicide.

Abstract A sensitive electrochemical sensor was successfully developed based on a glassy carbon (GC) electrode modified by a combination of multi-walled carbon nanotubes (MWCNT) with beta-cyclodextrin (beta-CD) incorporated in a polyaniline film, and applied to detect and determine the fungicide pyrimethanil in pome fruit (apples). The beta-CD/MWCNT modified GC electrode displayed a detection limit of 1.04 mu M (0.21 mg/kg) which is below the maximum residue levels set for pyrimethanil in pome fruit and citrus fruit by EU regulations. The results indicate that the (beta-CD/MWCNT modified GC electrode exhibits efficient electrocatalytic oxidation of pyrimethanil with high reproducibility, repeatability and stability. Furthermore, the obtained results were in excellent agreement with those obtained using an established HPLC procedure.

Abstract Detection and quantification of cocaine is a key tool in fields such as police apprehensions and the fight against drug trafficking. Thus, a simple, fast and inexpensive electroanalytical methodology for the determination of cocaine in seized street samples has been developed, employing linear sweep voltammetry. The method is based on the use of a glassy carbon (GC) electrode modified by a combination of multi-walled carbon nanotubes (MWCNT) with beta-cyclodextrin (beta-CD) incorporated in a polyaniline film. The proposed method shows high reproducibility, repeatability and specificity. Under optimal conditions, the beta-CD/MWCNT-modified GC electrode gives a detection limit of 1.02 mu M cocaine. The results obtained are in good agreement with those obtained by the high-performance liquid chromatography reference method. The new methodology proposed has excellent potential as the basis of a portable analytical sensor for on-site screening of cocaine in seized street samples.