RESUMO
Phytopathogenic fungi are among the main causes of productivity losses in agriculture. To date, synthetic chemical pesticides, such as hydroxyanilides, anilinopyrimidines and azole derivatives, represent the main treatment tools for crop plant defence. However, the large and uncontrolled use of these substances has evidenced several side effects, namely the resistance to treatments, environmental damage and human health risks. The general trend is to replace chemicals with natural molecules in order to reduce these side effects. Moreover, the valorisation of agri-food industry by-products through biotransformation processes represents a sustainable alternative to chemical synthesis in several sectors. This research is aimed at comparing the anti-phytopathogenic activity of waste bovine and porcine bile with secosteroids obtained by biotransformation of bile acids with Rhodococcus strains. The ultimate goal is to apply these natural products on food crops affected by phytopathogenic fungi.
Assuntos
Agricultura , Ácidos e Sais Biliares , Animais , Biotransformação , Bovinos , Produtos Agrícolas , Fungos , SuínosRESUMO
Biocatalyzed synthesis can be exploited to produce high-value products, such as prodrugs. The replacement of chemical approaches with biocatalytic processes is advantageous in terms of environmental prevention, embracing the principles of green chemistry. In this work, we propose the covalent attachment of xylitol to ibuprofen to produce an IBU-xylitol ester prodrug. Xylitol was chosen as a hydrophilizer for the final prodrug, enhancing the water solubility of ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) extensively used as an analgesic, anti-inflammatory, and antipyretic. Despite being the third-most-prescribed medicine in the world, the aqueous solubility of ibuprofen is just 21 mg/L. This poor water solubility greatly limits the bioavailability of ibuprofen. We aimed to functionalize ibuprofen with xylitol using the reusable immobilized N435 biocatalyst. Instead of a biphasic media, we proposed a monophasic reaction environment. The characterization of the IBU-xylitol ester was performed by 1H, 13C-NMR, DEPT, COSY, HMQC, HMBC, FTIR, and MS spectroscopy. Preliminary in vitro tests showed that this enzymatically synthesized prodrug of ibuprofen reduced the expression of the interleukin 8 genes in human bronchial epithelial cells (IB3-1) from cystic fibrosis (CF) patients.
Assuntos
Ibuprofeno/química , Pró-Fármacos/química , Xilitol/química , Analgésicos/química , Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Biocatálise , Disponibilidade Biológica , Linhagem Celular , Fibrose Cística/tratamento farmacológico , Ésteres/química , Humanos , Ibuprofeno/farmacologia , Pró-Fármacos/farmacologia , Solubilidade , Água/químicaRESUMO
Nowadays, the most important tool to evaluate the environmental impact of both petro-plastics and bioplastics is the life cycle analysis (LCA). LCA determines the overall impact on the environment by defining, calculation and analyzing all the input and output directly related to production, utilization, and disposal of a product or a process. In this work, a LCA (cradle to grave) of bottles for drinking water was developed on three scenarios: polyethylene terephthalate (PET) bottles, as conventional packaging material for outdoor drinking water, polylactic acid (PLA) bottles, as alternative and innovative biodegradable packaging and aluminum bottle, as reusable and almost infinitely refilling packaging. As a result of LCA, ten impacts categories have been accounted for, among which the global warming potential (GWP, measured as kgCO2 eq), the eutrophication potential (EP, measured as kgPO4 eq.), human and eco-toxicity (HTP and ETP, measured as kg 1,4-DB eq.). The average drinking water consumption in Italy has been estimated in 1.5 L per day, corresponding to three 500 ml-plastic bottles and 1 refillable aluminum bottle. LCA has been firstly applied to a single bottle production and use, then to the daily and annual bottles consumption. PET bottles production and use assure the lower environmental impacts compared to PLA bottles, burdened by agricultural phase for corn cultivation, and to aluminum bottles, when the every-day washing with hot water or water and soap is comprehended. Moreover, including the end-of-life options into the analysis, PET recycling permits to reduce up to about 30% the GWP, whereas PLA composting does not lead to any GWP savings. In this study, aluminum bottle has been considered reusable for 2.5 years. The microbiological quality of water in one-way PET and PLA bottles has been compared with the refillable bottle rinsing with hot water and soap and only hot water, highlighting that the level of contamination is alarmingly increased in the latter case.
Assuntos
Água Potável , Polietilenotereftalatos , Alumínio , Humanos , Itália , Plásticos , PoliésteresRESUMO
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) introduced in the 1960s and widely used as an analgesic, anti-inflammatory, and antipyretic. In its acid form, the solubility of 21 mg/L greatly limits its bioavailability. Since the bioavailability of a drug product plays a critical role in the design of oral administration dosage, this study investigated the enzymatic esterification of ibuprofen as a strategy for hydrophilization. This work proposes an enzymatic strategy for the covalent attack of highly hydrophilic molecules using acidic functions of commercially available bioactive compounds. The poorly water-soluble drug ibuprofen was esterified in a hexane/water biphasic system by direct esterification with sorbitol using the cheap biocatalyst porcine pancreas lipase (PPL), which demonstrated itself to be a suitable enzyme for the effective production of the IBU-sorbitol ester. This work reports the optimization of the esterification reaction.
Assuntos
Biocatálise , Meios de Cultura/química , Ibuprofeno/química , Sorbitol/química , Animais , Esterificação , Hidrólise , Ibuprofeno/síntese química , Lipase/metabolismo , Solventes , Especificidade por Substrato , Suínos , Temperatura , Fatores de Tempo , Água/químicaRESUMO
Bile acids (BAs) are a family of steroids synthesized from cholesterol in the liver. Among bile acids, ursodeoxycholic acid (UDCA) is the drug of choice for treating primary biliary cirrhosis and dissolving cholesterol gallstones. The clinical effectiveness of UDCA includes its choleretic activity, the capability to inhibit hydrophobic bile acid absorption by the intestine under cholestatic conditions, reducing cholangiocyte injury, stimulation of impaired biliary output, and inhibition of hepatocyte apoptosis. Despite its clinical effectiveness, UDCA is poorly soluble in the gastro-duodeno-jejunal contents, and pharmacological doses of UDCA are not readily soluble in the stomach and intestine, resulting in incomplete absorption. Indeed, the solubility of 20 mg/L greatly limits the bioavailability of UDCA. Since the bioavailability of drug products plays a critical role in the design of oral administration dosages, we investigated the enzymatic esterification of UDCA as a strategy of hydrophilization. Therefore, we decided to enzymatically synthesize a glyceric ester of UDCA bile acid to produce a more water-soluble molecule. The esterification reactions between UDCA and glycerol were performed with an immobilized lipase B from Candida antarctica (Novozym 435) in solvent-free and solvent-assisted systems. The characterization of the UDCA-monoglyceride, enzymatically synthesized, has been performed by 1H-NMR, 13C-NMR, COSY, HSQC, HMBC, IR, and MS spectroscopy.
Assuntos
Enzimas Imobilizadas/química , Proteínas Fúngicas/química , Monoglicerídeos/química , Pró-Fármacos/síntese química , Ácido Ursodesoxicólico/química , Basidiomycota/enzimologia , Catálise , Cromatografia Líquida de Alta Pressão , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo , Esterificação , Proteínas Fúngicas/metabolismo , Glicerol/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Solubilidade , Solventes/química , TemperaturaRESUMO
Cortisone is a steroid widely used as an anti-inflammatory drug able to suppress the immune system, thus reducing inflammation and attendant pain and swelling at the site of an injury. Due to its numerous side effects, especially in prolonged and high-dose therapies, the development of the pharmaceutical industry is currently aimed at finding new compounds with similar activities but with minor or no side effects. Biotransformations are an important methodology towards more sustainable industrial processes, according to the principles of "green chemistry". In this work, the biotransformation of cortisone with Rhodococcus rhodnii DSM 43960 to give two new steroids, i.e., 1,9ß,17,21-tetrahydoxy-4-methyl-19-nor-9ß-pregna-1,3,5(10)-trien-11,20-dione and 1,9ß,17,20ß,21-pentahydoxy-4-methyl-19-nor-9ß-pregna-1,3,5(10)-trien-11-one, is reported. These new steroids have been fully characterized.
Assuntos
Anti-Inflamatórios/síntese química , Anti-Inflamatórios/metabolismo , Cortisona/química , Rhodococcus/química , Esteroides/síntese química , Esteroides/metabolismo , Biotransformação , Química VerdeRESUMO
Prednisone and prednisolone are steroids widely used as anti-inflammatory drugs. Development of the pharmaceutical industry is currently aimed at introducing biotechnological processes and replacing multiple-stage chemical syntheses. In this work we evaluated the ability of bacteria belonging to the Rhodococcus genus to biotransform substrates, such as cortisone and hydrocortisone, to obtain prednisone and prednisolone, respectively. These products are of great interest from a pharmaceutical point of view as they have higher anti-inflammatory activity than the starting substrates. After an initial lab-scale screening of 13 Rhodococcus strains, to select the highest producers of prednisone and prednisolone, we reported the 200 ml-batch scale-up to test the process efficiency and productivity of the most promising Rhodococcus strains. R. ruber, R. globerulus and R. coprophilus gave the Δ1-dehydrogenation products of cortisone and hydrocortisone (prednisone and prednisolone) in variable amounts. In these biotransformations, the formation of products with the reduced carbonyl group in position C20 of the lateral chain of the steroid nucleus was also observed (i.e., 20ß-hydroxy-prednisone and 20ß-hydroxy-prednisolone). The yields, the absence of collateral products, and in some cases the absence of starting products allow us to say that cortisone and hydrocortisone are partly degraded.
Assuntos
Anti-Inflamatórios/metabolismo , Cortisona/metabolismo , Hidrocortisona/metabolismo , Prednisolona/metabolismo , Prednisona/metabolismo , Rhodococcus/metabolismo , Anti-Inflamatórios/química , Biotransformação , Catálise , Cortisona/química , Hidrocortisona/química , Prednisolona/química , Prednisona/química , Esteroides/química , Esteroides/metabolismoRESUMO
Recently, the use of disinfectants has been becoming a diffused and sometimes indiscriminate practice of paramount importance to limit the spreading of infections. The control of microbial contamination has now been concentrated on the use of traditional agents (i.e., hypochlorite, ozone). However, their prolonged use can cause potential treats, for both human health and environment. Currently, low-impact but effective biocides that are prepared in a way that avoids waste, with a very low toxicity, and safe and easy to handle and store are strongly needed. In this study, produced electrochemically activated hypochlorous (HOCl) acid solutions are investigated and proposed, integrated in a scrubbing machine for floor cleaning treatment. Such an innovative machine has been used for floor cleaning and sanitation in order to evaluate the microbial charge and organic dirt removal capacity of HOCl in comparison with a machine charged with traditional Ecolabel standard detergent. The potential damage on floor materials has also been investigated by means of Scanning Electron Microscope (SEM). A comparative Life Cycle Assessment (LCA) analysis has been carried out for evaluating the sustainability of the use of the HOCl-based and detergent-based machine.
Assuntos
Desinfetantes , Saneamento , Humanos , Detergentes , Ácido Hipocloroso , DifusãoRESUMO
The COVID-19 pandemic has underlined the importance of disinfectants as tools to prevent and fight against coronavirus spreading. An ideal disinfectant and sanitizer must be nontoxic to surface contact, noncorrosive, effective, and relatively inexpensive as it is hypochlorous acid (HOCl). The present work intended to evaluate, on different surfaces, the bactericidal and virucidal effectiveness of nebulized HOCl and test its safety usage in 2D and 3D skin and lung models. Our data showed that HOCl at the dose of 300 ppm did not affect cellular and tissue viability, not their morphology. The HOCl bactericidal properties varies with the surface analyzed: 69% for semi-porous, 96-99.9% for flat and porous. This discrepancy was not noticed for the virucidal properties. Overall, this study showed that nebulized HOCl can prevent virus and bacteria growth without affecting lung and skin tissues, making this compound a perfect candidate to sanitize indoor environments.