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1.
Appl Microbiol Biotechnol ; 108(1): 379, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888798

RESUMEN

The transition towards a sustainable model, particularly the circular economy, emphasizes the importance of redefining waste as a valuable resource, paving the way for innovative upcycling strategies. The olive oil industry, with its significant output of agricultural waste, offers a promising avenue for high-value biomass conversion into useful products through microbial processes. This study focuses on exploring new, high-value applications for olive leaves waste, utilizing a biotechnological approach with Lactobacillus casei for the production of second-generation lactic acid. Contrary to initial expectations, the inherent high polyphenol content and low fermentable glucose levels in olive leaves posed challenges for fermentation. Addressing this, an enzymatic hydrolysis step, following a preliminary extraction process, was implemented to increase glucose availability. Subsequent small-scale fermentation tests were conducted with and without nutrient supplements, identifying the medium that yielded the highest lactic acid production for scale-up. The scaled-up batch fermentation process achieved an enhanced conversion rate (83.58%) and specific productivity (0.26 g/L·h). This research confirms the feasibility of repurposing olive waste leaves for the production of lactic acid, contributing to the advancement of a greener economy through the valorization of agricultural waste. KEY POINTS: • Olive leaves slurry as it did not allow L. casei to ferment. • High concentrations of polyphenols inhibit fermentation of L. casei. • Enzymatic hydrolysis combined to organosolv extraction is the best pretreatment for lactic acid production starting from leaves and olive pruning waste.


Asunto(s)
Fermentación , Ácido Láctico , Lacticaseibacillus casei , Olea , Aceite de Oliva , Hojas de la Planta , Ácido Láctico/metabolismo , Lacticaseibacillus casei/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Aceite de Oliva/metabolismo , Glucosa/metabolismo , Hidrólisis , Residuos Industriales , Polifenoles/metabolismo , Biomasa
2.
Mar Drugs ; 22(3)2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38535463

RESUMEN

This study reports the first detection of the marine neurotoxin pinnatoxin-G (PnTX-G) in clams collected in the northwestern Adriatic Sea (Italy). It also represents the first report of the potential toxin-producing dinoflagellate, Vulcanodinium rugosum, in Italian seas. This result, from the coasts of the Emilia-Romagna Region, indicates a successful colonization process, reflecting conditions in France where V. rugosum was initially documented. In this case, the concentration of PnTXs was very low, making further sampling necessary to fully understand the extent of the phenomenon. Discussions on the need to obtain more data to support a proper risk assessment and the need to implement a monitoring program that includes emerging marine biotoxins are also included.


Asunto(s)
Alcaloides , Dinoflagelados , Compuestos de Espiro , Humanos , Francia , Italia
3.
J Enzyme Inhib Med Chem ; 38(1): 2270180, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37850364

RESUMEN

A novel library of human carbonic anhydrase (hCA) inhibitors based on the 2-sulfanilamido[1,2,4]triazolo[1,5-a]pyrimidine skeleton modified at its 7-position was prepared by an efficient convergent procedure. These derivatives were evaluated in vitro for their inhibition properties against a representative panel of hCA isoforms (hCA I, II, IV, IX, and XII). The target tumour-associated isoforms hCA IX and XII were potently inhibited with KIs in the low nanomolar range of 5-96 nM and 4-72 nM, respectively. Compounds 1d, 1j, 1v, and 1x were the most potent hCA IX inhibitors with KIs of 5.1, 8.6, 4.7, and 5.1 nM, respectively. Along with derivatives 1d and 1j, compounds 1r and 1ab potently inhibited hCA XII isoform with KIs in a single-digit nanomolar range of 8.8, 5.4, 4.3, and 9.0 nM, respectively. Compounds 1e, 1m, and 1p exhibited the best selectivity against hCA IX and hCA XII isoforms over off-target hCA II, with selectivity indexes ranging from 5 to 14.


Asunto(s)
Antígenos de Neoplasias , Anhidrasa Carbónica II , Humanos , Anhidrasa Carbónica II/metabolismo , Relación Estructura-Actividad , Anhidrasa Carbónica IX/metabolismo , Anhidrasa Carbónica I/metabolismo , Isoformas de Proteínas , Sulfanilamidas , Inhibidores de Anhidrasa Carbónica/farmacología , Estructura Molecular
4.
Phytother Res ; 37(7): 2915-2938, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36879409

RESUMEN

The understanding of the use of Magnolia officinalis L. (Magnoliaceae) as a possible dietary supplement for supporting the treatment of airway pathologies might be of clinical interest. Two commercially available bark extracts (M. officinalis extract [MOE]) were characterized by quantitation in honokiol and magnolol content by means of high-performance liquid chromatography with UV detection. MOE effects, as well as those of the reference compounds per se, on some targets connected to airway pathologies (antibacterial- and lung and trachea relaxing- activities) were investigated. Results showed that MOE possessed interesting antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pneumoniae. This was accompanied by a spasmolytic and antispasmodic activity, possibly owing to its ability to concurrently modulate different targets such as H1 -, ß2 - and muscarinic receptors and l-type calcium channels involved in bronchodilation. All these effects were directly related to the MOE content in honokiol and magnolol. In conclusion, the properties of MOE highlighted here strongly encourage its application as dietary supplement in the treatment of airway diseases.


Asunto(s)
Lignanos , Magnolia , Enfermedades Respiratorias , Humanos , Magnolia/química , Medicina Tradicional China , Corteza de la Planta/química , Lignanos/farmacología , Compuestos de Bifenilo , Extractos Vegetales/química
5.
Molecules ; 28(19)2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37836777

RESUMEN

A comparative study on essential oils extracted from Mentha suaveolens Ehrh. from Italy is reported. Two extraction procedures were investigated: hydrodistillation and steam distillation, carried out as a continuous and fractionated procedure. Fresh and dried plant material from two harvests was used. The hydrodistillation method yielded a higher amount of essential oil. The dried plant was significantly richer in essential oil per kg of starting plant material. Gas chromatography-mass spectrometry analysis of 112 samples showed that the essential oils belong to the piperitenone oxide-rich chemotype. In addition, piperitenone, p-cymen-8-ol, and limonene were among the most abundant compounds in the different samples. A higher amount of piperitenone oxide was obtained by hydrodistillation, while steam distillation gave a higher percentage of piperitenone and limonene. The essential oils were characterized for their anti-Candida albicans activity; higher potency was observed for the samples rich in piperitenone oxide, with MIC values ranging from 0.39 to 0.78 mg·mL-1 (0.039% and 0.078% p/v). The results of this work provide a deep insight into the methodology of essential oil extraction and the associated chemical variability of M. suaveolens Ehrh. Some of the essential oils are potent against C. albicans and could be considered for potential use in therapy.


Asunto(s)
Mentha , Aceites Volátiles , Aceites Volátiles/farmacología , Aceites Volátiles/química , Candida , Limoneno , Mentha/química , Destilación , Vapor , Candida albicans
6.
Microb Cell Fact ; 21(1): 250, 2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-36419154

RESUMEN

Cortisone is a metabolite belonging to the corticosteroid class that is used pharmaceutically directly as a drug or prodrug. In addition to its large consumption, its use is linked to several side effects, so pharmaceutical research aims to develop effective drugs with low or no side effects, alternative compounds to cortisone are part of an active investment in ongoing research on drug discovery. Since biotransformation can be considered a source of new molecules with potential therapeutic use, the present work focuses on a preliminary in vitro study aimed at evaluating the mutagenic, anti-inflammatory, antioxidant and neuroprotective activity of SCA and SCB molecules obtained from the biotransformation of cortisone using Rh. Rhodnii strain DSM 43960. The results obtained are very encouraging due to the safety of biotransformed compounds with reference to genotoxicity checked by Ames test, to the very high antioxidant capacity and to the anti-inflammatory activity. In fact, thecompounds inhibited both the TNFα-stimulated expression and secretion of NFkB target cytokines, and COX activity, and can activate the glucocorticoid receptor. Finally SCA and SCB exhibited neuroprotective properties.


Asunto(s)
Cortisona , Antioxidantes/farmacología , Biotransformación , Esteroides , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
7.
Molecules ; 28(1)2022 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-36615480

RESUMEN

A current trend of research in the health field is toward the discovery of multifunctional compounds, capable of interacting with multiple biological targets, thus simplifying multidrug therapies and improving patient compliance. The aim of this work was to synthesize new multifunctional chemical entities bearing a benzothiazole nucleus, a structure that has attracted increasing interest for the great variety of biological actions that it can perform, and already used as a scaffold in several multifunctional drugs. Compounds are reported, divided into two distinct series, synthetized and tested in vitro for the antioxidant, and include UV-filtering and antitumor activities. DPPH and FRAP tests were chosen to outline an antioxidant activity profile against different radical species. The UV-filtering activity was investigated, pre- and post-irradiation, through evaluation of a O/W sunscreen standard formulation containing 3% of the synthetic compounds. The antitumor activity was investigated both on human melanoma cells (Colo-38) and on immortalized human keratinocytes as a control (HaCat). A good antiproliferative profile in terms of IC50 was chosen as a mandatory condition to further investigate apoptosis induction as a possible cytotoxicity mechanism through the Annexin V test. Compound BZTcin4 was endowed with excellent activity and a selectivity profile towards Colo-38, supported by a good antioxidant capacity and an excellent broad-spectrum photoprotective profile.


Asunto(s)
Antineoplásicos , Antioxidantes , Humanos , Antioxidantes/química , Línea Celular Tumoral , Antineoplásicos/química , Protectores Solares/farmacología , Protectores Solares/química , Benzotiazoles/química , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular
8.
Molecules ; 26(20)2021 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-34684861

RESUMEN

Scientific investigation on essential oils composition and the related biological profile are continuously growing. Nevertheless, only a few studies have been performed on the relationships between chemical composition and biological data. Herein, the investigation of 61 assayed essential oils is reported focusing on their inhibition activity against Microsporum spp. including development of machine learning models with the aim of highlining the possible chemical components mainly related to the inhibitory potency. The application of machine learning and deep learning techniques for predictive and descriptive purposes have been applied successfully to many fields. Quantitative composition-activity relationships machine learning-based models were developed for the 61 essential oils tested as Microsporum spp. growth modulators. The models were built with in-house python scripts implementing data augmentation with the purpose of having a smoother flow between essential oils' chemical compositions and biological data. High statistical coefficient values (Accuracy, Matthews correlation coefficient and F1 score) were obtained and model inspection permitted to detect possible specific roles related to some components of essential oils' constituents. Robust machine learning models are far more useful tools to reveal data augmentation in comparison with raw data derived models. To the best of the authors knowledge this is the first report using data augmentation to highlight the role of complex mixture components, in particular a first application of these data will be for the development of ingredients in the dermo-cosmetic field investigating microbial species considering the urge for the use of natural preserving and acting antimicrobial agents.


Asunto(s)
Antiinfecciosos/química , Aprendizaje Automático , Microsporum/efectos de los fármacos , Aceites Volátiles/química , Antiinfecciosos/farmacología , Arthrodermataceae/efectos de los fármacos , Mezclas Complejas/química , Mezclas Complejas/farmacología , Recolección de Datos , Aceites Volátiles/farmacología , Filogenia , Relación Estructura-Actividad
9.
Bioorg Chem ; 94: 103396, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31677860

RESUMEN

Three series of arylbenzimidazole derivatives 3-40, 45 have been simply synthesized and tested for their antioxidant capacity. The 2-arylbenzimidazoles were tested against various radicals by the DPPH, FRAP and ORAC tests and showed different activity profiles. It has been observed that the number and position of the hydroxy groups on the 2-aryl portion and the presence of a diethylamino group or a 2-styryl group are related to a good antioxidant capacity. Furthermore, benzimidazoles showed satisfactory SPF values ​​in vitro compared to the commercial PBSA filter, proving to have a good photoprotective profile. In particular, 2-arylbenzimidazole-5-sulphonic acids 15 and 38, the 2-styryl-benzimidazole 45 showed broad spectrum solar protection against UVA and UVB rays. The antiproliferative effect of the benzimidazoles was tested on human skin melanoma Colo-38 cells. The styrylbenzimidazole 45 exhibited antiproliferative effect at low micromolar concentration against Colo-38 cells and very low antiproliferative activity on normal HaCat keratinocyte cells.


Asunto(s)
Antineoplásicos/farmacología , Antioxidantes/farmacología , Bencimidazoles/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antioxidantes/síntesis química , Antioxidantes/química , Bencimidazoles/síntesis química , Bencimidazoles/química , Compuestos de Bifenilo/antagonistas & inhibidores , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Picratos/antagonistas & inhibidores , Relación Estructura-Actividad
10.
Bioorg Chem ; 101: 103960, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32559579

RESUMEN

Oxidative stress is the product or aetiology of various multifactorial diseases; on the other hand, the development of multifunctional compounds is a recognized strategy for the control of complex diseases. To this end, a series of benzothiazole derivatives was synthesized and evaluated for their multifunctional effectiveness as antioxidant, sunscreen (filter), antifungal and antiproliferative agents. Compounds were easily synthesized via condensation reaction between 2-aminothiophenols and different benzaldehydes. SAR study, particularly in position 2 and 6 of benzothiazoles, led to the identification of 4g and 4k as very interesting potential compounds for the design of multifunctional drugs. In particular, compound 4g is the best blocker of hERG potassium channels expressed in HEK 293 cells exhibiting 60.32% inhibition with IC50 = 4.79 µM.


Asunto(s)
Benzotiazoles/química , Diseño de Fármacos , Antifúngicos/farmacología , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Células HEK293 , Humanos
11.
Int J Mol Sci ; 21(6)2020 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-32213974

RESUMEN

Cutaneous stem cells, gained great attention in the field of regenerative medicine as a potential therapeutic target for the treatment of skin and hair disorders and various types of skin cancers. Cutaneous stem cells play a key role in several processes like the renovation of skin structures in the condition of homeostasis and after injuries, the hair follicle growth and the reconstruction and production of melanocytes. Thus, gaining effective access to skin stem cells for therapeutic interventions that often involve active molecules with non-favorable characteristics for skin absorption is a valuable achievement. The topical route with high patient compliance and several other benefits is gaining increasing importance in basic and applied research. However, the major obstacle for topical drug delivery is the effective barrier provided by skin against penetration of the vast majority of exogenous molecules. The research in this field is focusing more and more on new strategies to circumvent and pass this barrier effectively. In this article the existing approaches are discussed considering physical and chemical methods along with utilization of novel drug delivery systems to enhance penetration of drugs to the skin. In particular, attention has been paid to studies finalized to the delivery of molecules to cutaneous stem cells with the aim of transferring signals, modulating their metabolic program, inducing physiological modifications and stem cell gene therapy.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Enfermedades de la Piel/tratamiento farmacológico , Células Madre/efectos de los fármacos , Administración Cutánea , Animales , Humanos , Piel/citología , Piel/efectos de los fármacos , Piel/metabolismo
12.
Molecules ; 25(18)2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-32967192

RESUMEN

In the search for scaffolds for multifunctional compounds we investigated the structure activity relationship of a class of benzimidazole derivatives bearing 5-membered ring. The newly synthesized and the already known compounds were divided into three classes that present different substituent at 5 position of the benzimidazole ring (-H, -COOH or -SO3H) and different heterocycle at position 2 (thiophene, furan or pyrrole). All the derivatives were synthesized and tested to determine their photoprotective profile against UV rays, in vitro antioxidant capacity against different radicals (DPPH and FRAP test), antifungal inhibitory activity (dermatophytes and Candida albicans), antiviral and antiproliferative activity. A Structure-Activity Relationship study indicated compound 10, bearing a pyrrole heterocycle on the benzimidazole ring, as the best multifunctional derivative of the series and as potential candidate for the development of drugs especially in case of melanoma.


Asunto(s)
Bencimidazoles/química , Bencimidazoles/farmacología , Protectores contra Radiación/química , Protectores contra Radiación/farmacología , Piel/efectos de los fármacos , Antifúngicos/química , Antifúngicos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Antivirales/química , Antivirales/farmacología , Candida albicans/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Humanos , Piel/efectos de la radiación , Relación Estructura-Actividad , Rayos Ultravioleta/efectos adversos
13.
Molecules ; 25(9)2020 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-32384805

RESUMEN

Induction of apoptosis is a common chemotherapeutic mechanism to kill cancer cells The thiazole system has been reported over the past decades as a building block for the preparation of anticancer agents. A novel series of 2-arylalkylamino-4-amino-5-(3',4',5'-trimethoxybenzoyl)-thiazole derivatives designed as dual inhibitors of tubulin and cyclin-dependent kinases (CDKs) were synthesized and evaluated for their antiproliferative activity in vitro against two cancer cell lines and, for selected highly active compounds, for interactions with tubulin and cyclin-dependent kinases and for cell cycle and apoptosis effects. Structure-activity relationships were elucidated for various substituents at the 2-position of the thiazole skeleton. Among the synthesized compounds, the most active analogues were found to be the p-chlorobenzylamino derivative 8e as well as the p-chloro and p-methoxyphenethylamino analogues 8f and 8k, respectively, which inhibited the growth of U-937 and SK-MEL-1 cancer cell lines with IC50 values ranging from 5.7 to 12.2 µM. On U-937 cells, the tested compounds 8f and 8k induced apoptosis in a time and concentration dependent manner. These two latter molecules did not affect tubulin polymerization (IC50 > 20 µM) nor CDK activity at a single concentration of 10 µM, suggesting alternative targets than tubulin and CDK for the compounds.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Tiazoles/síntesis química , Tiazoles/farmacología , Tubulina (Proteína)/química , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 9 Dependiente de la Ciclina/antagonistas & inhibidores , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Microtúbulos/efectos de los fármacos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad , Tiazoles/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacología
14.
Molecules ; 25(7)2020 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-32272719

RESUMEN

Two novel series of compounds based on the 4,5,6,7-tetrahydrothieno[2,3-c]pyridine and 4,5,6,7-tetrahydrobenzo[b]thiophene molecular skeleton, characterized by the presence of a 3',4',5'-trimethoxyanilino moiety and a cyano or an alkoxycarbonyl group at its 2- or 3-position, respectively, were designed, synthesized, and evaluated for antiproliferative activity on a panel of cancer cell lines and for selected highly active compounds, inhibition of tubulin polymerization, and cell cycle effects. We have identified the 2-(3',4',5'-trimethoxyanilino)-3-cyano-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivative 3a and its 6-ethoxycarbonyl homologue 3b as new antiproliferative agents that inhibit cancer cell growth with IC50 values ranging from 1.1 to 4.7 µM against a panel of three cancer cell lines. Their interaction with tubulin at micromolar levels leads to the accumulation of cells in the G2/M phase of the cell cycle and to an apoptotic cell death. The cell apoptosis study found that compounds 3a and 3b were very effective in the induction of apoptosis in a dose-dependent manner. These two derivatives did not induce cell death in normal human peripheral blood mononuclear cells, suggesting that they may be selective against cancer cells. Molecular docking studies confirmed that the inhibitory activity of these molecules on tubulin polymerization derived from binding to the colchicine site.


Asunto(s)
Antineoplásicos/química , Productos Biológicos/química , Piridinas/química , Moduladores de Tubulina/química , Tubulina (Proteína)/metabolismo , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Productos Biológicos/farmacología , Muerte Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colchicina/química , Ensayos de Selección de Medicamentos Antitumorales/métodos , Fase G2/efectos de los fármacos , Células HeLa , Humanos , Células K562 , Leucocitos Mononucleares/efectos de los fármacos , Ratones , Simulación del Acoplamiento Molecular/métodos , Piridinas/farmacología , Relación Estructura-Actividad
15.
Medicina (Kaunas) ; 56(3)2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-32110920

RESUMEN

Iran has a rich and diverse cultural heritage, consisting of a complex traditional medicine deeply rooted in the history of the territory that goes back to the Assyrian and Babylonian civilizations. The ethnomedical practices that can be identifiable nowadays derive from the experience of local people who have developed remedies against a wide range of diseases handing down the knowledge from generation to generation over the millennia. Traditional medicine practices represent an important source of inspiration in the process of the development of new drugs and therapeutic strategies. In this context, it is useful to determine the state of the art of ethnomedical studies, concerning the Iranian territory, and of scientific studies on plants used in traditional Iranian medicine. Data regarding 245 plants used in Iranian ethnomedical practices and scientific studies conducted on 89 plants collected in the Iranian territory have been reported. All of the scientific studies here reported draw inspiration from traditional medicine. The World Health Organization (WHO) has repeatedly called for an intensification of the scientific validation processes of traditional medicines intended as an important contribution to public health in various parts of the world. The process of study and validation of Iranian ethnomedical practices appears to be at an early stage.


Asunto(s)
Medicina Tradicional/métodos , Fitoterapia/métodos , Plantas Medicinales , Humanos , Irán
16.
Bioorg Chem ; 85: 568-576, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30825715

RESUMEN

Two series of indole derivatives 4-17, 20-22 were easily prepared and assayed for their radical-scavenging ability. Arylidene-1H-indole-2-carbohydrazones showed different extent antioxidant activity in DPPH, FRAP and ORAC assays. Good antioxidant activity is related to the number and position of hydroxyl groups on the arylidene moiety as well as to the presence of methoxy or 4-(diethylamino) group. On the contrary low antioxidant activity is showed by the isomeric 1H-indol-2-yl(methylene)-benzohydrazides. Furthermore, hydrazones 4-17 showed photoprotective capacities with satisfactory in vitro SPF as compared to the commercial PBSA sunscreen filter. The indole 16 and 17, showing the best antioxidant and photoprotective profile, were included in different formulation and their topical release was evaluated. Varying the formulation composition, it was possible to optimize skin adsorption and solubility of the active indole in the formulation. The antiproliferative effect of the hydrazones 4-17 was tested on human erythroleukemia K562 and melanoma Colo-38 cells. Hydrazones 11, 16 and 17 showed growth inhibition at sub micromolar concentrations on both cell lines. These results indicate indole hydrazones as potential multifunctional molecules especially in the treatment of neoplastic diseases being the good antioxidant properties of 16 and 17 correlated to their high antiproliferative activity.


Asunto(s)
Antineoplásicos/farmacología , Depuradores de Radicales Libres/farmacología , Hidrazonas/farmacología , Indoles/farmacología , Protectores Solares/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Humanos , Hidrazonas/síntesis química , Hidrazonas/química , Indoles/síntesis química , Indoles/química , Estructura Molecular , Relación Estructura-Actividad , Protectores Solares/síntesis química , Protectores Solares/química
17.
Molecules ; 24(8)2019 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-31027274

RESUMEN

The chemical composition and biological activity of essential oils isolated from the leaves of Siparuna aspera, Siparuna macrotepala, Piper leticianum, Piper augustum and the rhizome of Hedychium coronarium were evaluated. These species are used medicinally in different ways by the Amazonian communities that live near the Kutukú mountain range. Chemical studies revealed that the main components for the two Siparuna species were germacrene D, bicyclogermacrene, α-pinene, δ-cadinene, δ-elemene, α-copaene and ß-caryophyllene; for the two Piper species ß-caryophyllene, germacrene D, α-(E,E)-farnesene, ß-elemene, bicyclogermacrene, δ-cadinene and for H. coronarium 1,8-cineole, ß-pinene, α-pinene and α-terpineol. The antioxidant activity of all essential oils was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), photochemiluminescence (PCL) quantitative assays, and DPPH and ABTS bioautographic profiles, with different results for each of them. Antimicrobial activity studies were carried out on three yeasts, six Gram positive and four Gram negative bacteria, by means of the disc diffusion method. The essential oil of H. coronarium showed the most relevant results on L. grayi, K. oxytoca and S. mutans, P. augustum and P. leticianum on S. mutans. An antibacterial bioautographic test for H. coronarium was also carried out and highlighted the potential activity of terpinen-4-ol and 1,8-cineole.


Asunto(s)
Aceites Volátiles/análisis , Zingiberaceae/química , Antibacterianos/análisis , Antibacterianos/farmacología , Monoterpenos Bicíclicos , Compuestos Bicíclicos con Puentes/análisis , Compuestos Bicíclicos con Puentes/farmacología , Monoterpenos Ciclohexánicos , Ciclohexenos/análisis , Ciclohexenos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Monoterpenos/análisis , Monoterpenos/farmacología , Aceites Volátiles/farmacología , Bosque Lluvioso , Sesquiterpenos/análisis , Sesquiterpenos/farmacología
18.
Molecules ; 24(5)2019 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-30832446

RESUMEN

Biofilm resistance to antimicrobials is a complex phenomenon, driven not only by genetic mutation induced resistance, but also by means of increased microbial cell density that supports horizontal gene transfer across cells. The prevention of biofilm formation and the treatment of existing biofilms is currently a difficult challenge; therefore, the discovery of new multi-targeted or combinatorial therapies is growing. The development of anti-biofilm agents is considered of major interest and represents a key strategy as non-biocidal molecules are highly valuable to avoid the rapid appearance of escape mutants. Among bacteria, staphylococci are predominant causes of biofilm-associated infections. Staphylococci, especially Staphylococcus aureus (S. aureus) is an extraordinarily versatile pathogen that can survive in hostile environmental conditions, colonize mucous membranes and skin, and can cause severe, non-purulent, toxin-mediated diseases or invasive pyogenic infections in humans. Staphylococcus epidermidis (S. epidermidis) has also emerged as an important opportunistic pathogen in infections associated with medical devices (such as urinary and intravascular catheters, orthopaedic implants, etc.), causing approximately from 30% to 43% of joint prosthesis infections. The scientific community is continuously looking for new agents endowed of anti-biofilm capabilities to fight S. aureus and S epidermidis infections. Interestingly, several reports indicated in vitro efficacy of non-biocidal essential oils (EOs) as promising treatment to reduce bacterial biofilm production and prevent the inducing of drug resistance. In this report were analyzed 89 EOs with the objective of investigating their ability to modulate bacterial biofilm production of different S. aureus and S. epidermidis strains. Results showed the assayed EOs to modulated the biofilm production with unpredictable results for each strain. In particular, many EOs acted mainly as biofilm inhibitors in the case of S. epidermidis strains, while for S. aureus strains, EOs induced either no effect or stimulate biofilm production. In order to elucidate the obtained experimental results, machine learning (ML) algorithms were applied to the EOs' chemical compositions and the determined associated anti-biofilm potencies. Statistically robust ML models were developed, and their analysis in term of feature importance and partial dependence plots led to indicating those chemical components mainly responsible for biofilm production, inhibition or stimulation for each studied strain, respectively.


Asunto(s)
Biopelículas/efectos de los fármacos , Aceites Volátiles/química , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Humanos , Aprendizaje Automático , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/farmacología , Infecciones Estafilocócicas/microbiología , Staphylococcus/crecimiento & desarrollo , Staphylococcus/patogenicidad
19.
Molecules ; 24(24)2019 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-31842340

RESUMEN

The incidence of skin cancer is increasing both because of climate change and the increase in pollution than people's incorrect habits of sun exposure. In these regards, sunscreen and photoprotection are essential tools in consenting the benefits induced by safe solar light exposition and skin cancer prevention. In this work, a new class of sunscreen filter was synthesized by chemical combination of a physical filter (ZnO) and Oxisol (dihydroxyphenyl benzimidazole carboxylic acid), an antioxidant molecule with booster effect. In this work, a new class of filters with new properties was achieved by direct functionalization of particles surface. A full characterization of this multifunctional ingredient (ZnO-Ox) was conducted: Compared with the simple mixture, the new filter acts as a multifunctional molecule showing a higher Sun Protection Factor (SPF), a better cytotoxic profile (MTT and NRU assay), and anti-acne activity. A strong reduction of photocatalytic activity of ZnO was observed, also improving the safety profile.


Asunto(s)
Antioxidantes , Bencimidazoles , Protectores Solares , Rayos Ultravioleta/efectos adversos , Óxido de Zinc , Células 3T3 , Animales , Antioxidantes/química , Antioxidantes/farmacología , Bencimidazoles/química , Bencimidazoles/farmacología , Humanos , Ratones , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/prevención & control , Luz Solar/efectos adversos , Protectores Solares/química , Protectores Solares/farmacología , Óxido de Zinc/química , Óxido de Zinc/farmacología
20.
Molecules ; 23(3)2018 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-29543741

RESUMEN

Moringa oleifera has gained increasing popularity as a food supplement but not in the pharmaceutical and cosmetic area. The aim of this study was the preparation, characterization, and evaluation of extracts from the leaves of Moringa oleifera as a herbal sun care phytocomplex. Three different extracts of Moringa oleifera leaves, from Senegal, have been prepared and chemically characterized in the phenolic fraction by HPLC-DAD and Folin-Ciocalteu test. To explore photoprotective properties, an extensive evaluation of UV filtering, antioxidant (DPPH, FRAP, ORAC, PCL), and anti-hyperproliferative (human melanoma Colo38 cells) capacities have been conducted. Furthermore, a formulation study regarding cosmetic prototypes has been carried out in order to determine the Sun Protection Factor (SPF), which was assessed in vitro. The extracts were demonstrated to confer significant values of protection, with an SPF 2, that corresponds to a 50% protection against UV-B rays, at concentrations as low as 2% to 4%. Finally, the evaluation on potential irritation of the finished formulations was conducted by Patch Test and no significant irritant potential was observed. These evidence enlarged the already significant number of activities and potential uses of this plant, which is well-known for its importance in the medicinal and nutritional fields.


Asunto(s)
Antineoplásicos Fitogénicos/química , Antioxidantes/química , Moringa oleifera/química , Hojas de la Planta/química , Protectores Solares/química , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Masculino , Estructura Molecular , Extractos Vegetales/química , Polifenoles/química , Polifenoles/farmacología , Protectores Solares/farmacología
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