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1.
Artigo em Inglês | MEDLINE | ID: mdl-38925646

RESUMO

Virulence pathways in pathogenic bacteria are regulated by quorum sensing mechanisms, particularly biofilm formation through autoinducer production and sensing. In this study, the culture filtrate extracted from an edible mushroom, Agaricus subrutilescens, was fractionated to isolate a compound that inhibits biofilm formation. Four gram-negative bacteria (Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, and Enterobacter cloacae) and two gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) were used for the bioassay. The bioassay-guided chromatographic separations of the culture filtrate extract resulted in the isolation of the compound. Further, spectroscopic analyses revealed the identity of the compound as 2,2'-azoxybisbenzyl alcohol (ABA). The minimum inhibitory and sub-inhibitory concentrations of the compound were also determined. ABA was significantly effective in inhibiting biofilm formation in all tested bacteria, with half-maximal inhibitory concentrations of 3-11 µg/mL. Additionally, the bioactivity of ABA was confirmed through the bioassays for the inhibition of exopolysaccharide matrixes and autoinducer activities.

2.
J Appl Microbiol ; 135(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38802124

RESUMO

AIMS: Anthracnose caused by Colletotrichum species is one of the most devastating diseases of fruits and crops. We isolated and identified an antifungal compound from the mushroom Coprinus comatus and investigated its inhibitory potential against anthracnose disease-causing fungi with the goal of discovering natural products that can suppress anthracnose-caused plant disease. METHODS AND RESULTS: The culture filtrate of C. comatus was subjected to a bioassay-guided isolation of antifungal compounds. The active compound was identified as orsellinaldehyde (2,4-dihydroxy-6-methylbenzaldehyde) based on mass spectroscopy and nuclear magnetic resonance analyses. Orsellinaldehyde displayed broad-spectrum inhibitory activity against different plant pathogenic fungi. Among the tested Colletotrichum species, it exhibited the lowest IC50 values on conidial germination and germ tube elongation of Colletotrichum orbiculare. The compound also showed remarkable inhibitory activity against Colletotrichum gloeosporiodes. The staining of Colletotrichum conidia with fluorescein diacetate and propidium iodide demonstrated that the compound is fungicidal. The postharvest in-vivo detached fruit assay indicated that orsellinaldehyde suppressed anthracnose lesion symptoms on mango and cucumber fruits caused by C. gloeosporioides and C. orbiculare, respectively. CONCLUSIONS: Orsellinaldehyde was identified as a potent antifungal compound from the culture filtrate of C. comatus. The inhibitory and fungicidal activities of orsellinaldehyde against different Colletotrichum species indicate its potential as a fungicide for protecting various fruits against anthracnose disease-causing fungi.


Assuntos
Colletotrichum , Coprinus , Doenças das Plantas , Colletotrichum/efeitos dos fármacos , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Benzaldeídos/farmacologia , Antifúngicos/farmacologia , Fungicidas Industriais/farmacologia , Esporos Fúngicos/efeitos dos fármacos
3.
J Pestic Sci ; 48(4): 156-167, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38090223

RESUMO

The excessive use of chemical pesticides in agricultural fields for controlling plant pathogenic microorganisms harms human health, the environment, and other beneficial microorganisms in the soil and plants. To address this challenge, it is essential to isolate and discover bioactive compounds from biological resources that could inhibit plant pathogenic microorganisms. In this study, the culture filtrate of the edible mushroom Pleurotus ostreatus was subjected to bioassay-guided isolation, and two phthalide derivatives-4,6-dimethoxyphthalide (1) and 5,7-dimethoxyphthalide (2)-were identified, along with an oxindole compound-3-hydroxy-3-methyloxindole (3). The inhibitory activities of the three compounds were evaluated against four fungal and five bacterial pathogens. Remarkably, 1 and 2 exhibited the lowest IC50 values against the conidial germination and germ tube elongation of the rice blast fungus Pyricularia oryzae. However, their effectiveness against bacterial pathogens was relatively low. The (S) and (R)-enantiomers of 3-hydroxy-3-methyloxindole showed different activities against plant fungal pathogens and bacterial plant pathogens.

4.
J Fungi (Basel) ; 9(12)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38132787

RESUMO

This study investigates the impact of water quality, specifically elevated phosphate and zinc content, on the diversity and functional properties of mangrove fungal endophytes in two distinct mangrove forests. Mangrove plant performance is directly related to the presence of fungal leaf endophytes as these fungi could enhance plant health, resilience, and adaptability under stressed environmental conditions. Two distinct mangrove forest sites, one non-disturbed (ND) and one disturbed by aquaculture practices (D), were assessed for differences in water quality parameters. We further analyzed the fungal endophyte diversity associated with the leaves of a target host mangrove, Rhizophora mucronata Lamk., with the aim to elucidate whether fungal diversity and functional traits are linked to disturbances brought about by aquaculture practices and to characterize functional traits of selected fungal isolates with respect to phosphate (PO4) and zinc (Zn) solubilization. Contrary to expectations, the disturbed site exhibited a higher fungal diversity, challenging assumptions about the relationship between contamination and fungal community dynamics. Water quality, as determined by nutrient and mineral levels, emerged as a crucial factor in shaping both microbial community compositions in the phyllosphere of mangroves. From both sites, we isolated 188 fungal endophytes, with the ND site hosting a higher number of isolates and a greater colonization rate. While taxonomic diversity marginally differed (ND: 28 species, D: 29 species), the Shannon (H' = 3.19) and FAI (FA = 20.86) indices revealed a statistically significant increase in species diversity for fungal endophytes in the disturbed mangrove site as compared to the non-disturbed area (H' = 3.10, FAI = 13.08). Our chosen mangrove fungal endophytes exhibited remarkable phosphate solubilization capabilities even at elevated concentrations, particularly those derived from the disturbed site. Despite their proficiency in solubilizing zinc across a wide range of concentrations, a significant impact on their mycelial growth was noted, underscoring a crucial aspect of their functional dynamics. Our findings revealed a nuanced trade-off between mycelial growth and enzymatic production in fungal endophytes from ostensibly less contaminated sites, highlighting the relationship between nutrient availability and microbial activities. These insights provide a foundation for understanding the impact of anthropogenic pressures, specifically nutrient pollution, on mangrove-associated fungal endophytes.

5.
J Fungi (Basel) ; 9(11)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37998922

RESUMO

The rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics. Hence, there is a need to search for new sources of antibiotics that either exhibit novel structures or express a new mechanism of action. The lichen Usnea, with its wide range of unique, biologically potent secondary metabolites, may solve this problem. In this study, Usnea species were collected in the Northern Philippines, identified through combined morphological and biochemical characterization, and tested for antimicrobial activities against the multidrug-resistant ESKAPE pathogens, i.e., Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae, two standard antibiotic-sensitive test bacteria, and a yeast. A total of 46 lichen specimens were collected and later identified as Usnea baileyi (10), U. diffracta (10), U. glabrata (12), U. longissima (4), and U. rubicunda (10). The results show that the crude extracts of the Usnea species exhibited promising in vitro inhibitory activities against standard antibiotic-sensitive (E. faecalis ATCC 29212) and multidrug-resistant (methicillin-resistant S. aureus and E. faecalis) Gram-positive bacteria. Additionally, lichen compounds of representative specimens per species were identified and profiled using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The detection of lichen acids (LA) via HPLC showed the presence of 24 peaks of lichen acids. TLC-bioautography identified the bioactive lichen acids as alectronic acid, connorstictic acid, consalazinic acid, diffractaic acid, echinocarpic acid, erythrin acid, galbinic acid, hypoconstictic acid, hyposalazinic acid, hypostictic acid, lobaric acid, menegazzaic acid, micareic acid, pannarin, salazinic acid, stictic acid, and usnic acid. Our study highlighted the wide spectrum of opportunities for using lichens for the discovery of potential antimicrobial agents.

6.
Biosci Biotechnol Biochem ; 87(12): 1429-1441, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37667536

RESUMO

Antimicrobial compounds were purified from culture filtrates from 2 edible Pleurotus species. Using a bioassay-guided fractionation of the culture filtrate extracts, 3 compounds (1-3) were obtained from Pleurotus ostreatus, and another compound (4) was obtained from Pleurotus pulmonarius. Spectroscopic analysis revealed that 1-3 was identified as 5,7-dimethoxyphthalide, 4,6-dimethoxyphthalide, and cheimonophyllon E, respectively, while 4 were identified as pleuroton A. The minimum inhibitory concentration and minimum bactericidal concentration of these compounds were determined against 6 pathogenic bacterial species, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae. Compounds 2 and 4 were inhibitory against all tested bacteria, while 1 and 4 were inhibitory against 3 and 2 species, respectively. In addition, 1-4 inhibited tyrosinase, with IC50 values of 0.10-0.30 mg/mL, and α-glucosidase, with IC50 values of 0.12-0.54 mg/mL. However, their antioxidant capacities were marginal.


Assuntos
Agaricales , Anti-Infecciosos , Pleurotus , Sesquiterpenos , Agaricales/química , Anti-Infecciosos/farmacologia , Bactérias , Sesquiterpenos/química , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia
7.
Microorganisms ; 11(7)2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37512828

RESUMO

The persistence of beneficial microorganisms in the rhizosphere or surrounding soil following their application is a prerequisite for the effective interaction with the plant or indigenous microbial communities in the respective habitats. The goal of the study was to analyze the establishment and persistence of the applied beneficial Trichoderma harzianum (OMG16) strain in the maize root-associated soil depending on agricultural practice (soil management practice, N-fertilizer intensity) in a field experiment. A rapid identification of the inoculated strain OMG16 is essential for its monitoring. We used a culture-based approach coupled to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis for the rapid identification of the inoculated Trichoderma strain as part of the beneficial microbe consortium (BMc). We isolated 428 fungal isolates from eight treatments of the field experiment. Forty eight percent of the isolated fungi equivalent to 205 fungal isolates were identified as Trichoderma, of which 87% (=179 isolates) were obtained from the fields inoculated with BMc. Gene sequence analysis showed a high similarity of the MALDI-TOF MS-identified Trichoderma, with that of the inoculated Trichoderma harzianum OMG16 confirming the re-isolation of the added beneficial fungus. This study highlighted the use of MALDI-TOF MS analysis as a quick, cost-effective detection and efficient monitoring tool for microbial-based bioinoculants in the field.

8.
Trends Mol Med ; 29(3): 173-187, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36585352

RESUMO

Biodiversity is the measure of the variation of lifeforms in a given ecological system. Biodiversity provides ecosystems with the robustness, stability, and resilience that sustains them. This is ultimately essential for our survival because we depend on the services that natural ecosystems provide (food, fresh water, air, climate, and medicine). Despite this, human activity is driving an unprecedented rate of biodiversity decline, which may jeopardize the life-support systems of the planet if no urgent action is taken. In this article we show why biodiversity is essential for human health. We raise our case and focus on the biomedicine services that are enabled by biodiversity, and we present known and novel approaches to promote biodiversity conservation.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Humanos , Biodiversidade , Água Doce
9.
Plants (Basel) ; 11(3)2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35161404

RESUMO

Numerous reports confirm the positive effect of biochar application on soil properties and plant development. However, the interaction between root-associated beneficial microbes and different types of biochar is not well understood. The objective of this study was to evaluate the plant growth of lettuce after the application of three types of biochar in loamy, sandy soil individually and in combination with plant-beneficial microbes. Furthermore, total microbial activity in rhizosphere soil of lettuce was measured by means of fluorescein diacetate (FDA) hydrolase and enzyme activities linked to carbon, nitrogen, and phosphorus cycling. We used three types of biochar: (i) pyrolysis char from cherry wood (CWBC), (ii) pyrolysis char from wood (WBC), and (iii) pyrolysis char from maize (MBC) at 2% concentration. Our results showed that pyrolysis biochars positively affected plant interaction with microbial inoculants. Plant dry biomass grown on soil amended with MBC in combination with Klebsiella sp. BS13 and Klebsiella sp. BS13 + Talaromyces purpureogenus BS16aPP inoculants was significantly increased by 5.8% and 18%, respectively, compared to the control plants. Comprehensively, interaction analysis showed that the biochar effect on soil enzyme activities involved in N and P cycling depends on the type of microbial inoculant. Microbial strains exhibited plant growth-promoting traits, including the production of indole 3-acetic-acid and hydrogen cyanide and phosphate-solubilizing ability. The effect of microbial inoculant also depends on the biochar type. In summary, these findings provide new insights into the understanding of the interactions between biochar and microbial inoculants, which may affect lettuce growth and development.

10.
J Org Chem ; 87(4): 1996-2011, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-34355895

RESUMO

BMS-813160 is a pharmaceutical entity currently in development at Bristol Myers Squibb. Its defining structural feature is a unique chiral all cis triamino cyclohexane core. Medicinal and process chemistry groups at BMS have previously published synthesis strategies for chemotypes similar to the target molecule, but a streamlined approach amenable for longer-term supply was necessary. A new synthetic route was conceptualized, experimentally investigated, and determined to meet the criteria for efficiency that addressed key limitations of previous approaches. Adopting/optimizing the Trost asymmetric allylic amination desymmetrization methodology was a key tool used to produce a synthesis intermediate with high optical purity. In addition, developing a tandem Mannich-aza-Michael reaction to obviate the need for a Curtis/acylation sequence and a novel reductive amination/thermal lactamization to circumvent Freidinger-type pyrrolidone preparation are some of the synthesis improvements that enabled access to the target molecule to fulfill long-term supply requirements.


Assuntos
Catálise , Aminação , Pirazóis , Estereoisomerismo , Triazinas
11.
J Fungi (Basel) ; 7(7)2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34356951

RESUMO

The culture-based approach was used to characterize the fungal endophytes associated with the coralloid roots of the endemic Cycas debaoensis and Cycas fairylakea from various population sites in China. We aim to determine if the assemblages of fungal endophytes inside these endemic plant hosts are distinct and could be explored for bioprospecting. The isolation method yielded a total of 284 culturable fungal strains. Identification based on the analysis of the internal transcribed spacer (ITS) rDNA showed that they belonged to two phyla, five classes, eight orders and 22 families. At least 33 known genera and 62 different species were confirmed based on >97% ITS sequence similarity. The most frequent and observed core taxa in the two host species regardless of their population origin were Talaromyces, Penicillium, Fusarium, Pochonia and Gliocladiopsis. Seventy percent was a rare component of the fungal communities with only one or two recorded isolates. Contrary to common notions, diversity and fungal richness were significantly higher in C. debaoensis and C. fairylakea collected from a botanical garden, while the lowest was observed in C. debaoensis from a natural habitat; this provides evidence that garden management, and to a minor extent, ex-situ conservation practice, could influence fungal endophyte communities. We further selected nineteen fungal isolates and screened for their antagonistic activities via a co-cultivation approach against the phytopathogens, Diaporthe sp. and Colletotrichum sp. Among these, five isolates with high ITS similarity matches with Hypoxylon vinosupulvinatum (GD019, 99.61%), Penicillium sp. (BD022, 100%), Penicillifer diparietisporus (GD008, 99.46%), Clonostachys rogersoniana (BF024, 99.46%) and C. rosea (BF011, 99.1%), which showed exceptional antagonistic activities against the phytopathogenic fungi with a significant inhibition rate of 70-80%. Taken together, our data presented the first and most comprehensive molecular work on culturable fungal endophytes associated with the coralloid roots of cycads. Our study also demonstrated that about 5% of fungal endophytes were not detected by the high-throughput sequencing approach, implying the equal importance of a culture-dependent approach to study fungal communities of cycads. We further highlighted the potential role of endemic and rare plants to discover and isolate unique plant-associated fungal taxa with excellent biocontrol properties.

12.
J Fungi (Basel) ; 7(8)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34436130

RESUMO

Nickel contamination is a serious environmental issue that requires immediate action. In this study, 23 strains of Trichoderma were isolated from terrestrial and marine environments and identified using a polyphasic approach of morphological characterization and ITS gene sequence analysis. The Trichoderma strains were tested for their tolerance and biosorption of nickel. Our results showed the growth of all Trichoderma strains on Trichoderma Selective Medium (TSM) with 50-1200-ppm nickel, indicating their tolerance of this heavy metal even at a relatively high concentration. Six Trichoderma strains (three isolated from terrestrial substrates and three from marine substates) had the highest radial growth on TSM with 50-ppm Ni. Among these fungal isolates, Trichoderma asperellum (S03) isolated from soil exhibited the best growth after 2 days of incubation. For the biosorption of nickel, the accumulation or uptake efficiency by the six selected Trichoderma was determined in Potato Dextrose Broth (PDB) supplemented with 50-ppm Ni using a Flame Atomic Absorption Spectrophotometer (AAS). The percent uptake efficiency of the three strains of T. asperellum (S03, S08, and LL14) was computed to be up to 66%, while Trichoderma virens (SG18 and SF22) and Trichoderma inhamatum (MW25) achieved up to 68% uptake efficiency. Observation of the Trichoderma strains with Scanning Electron Microscopy (SEM) before and after the absorption of nickel showed very minimal damage on the hyphal and conidial surface morphology, but changes in the colonial characteristics were observed. Our study highlighted the potential of terrestrial and marine strains of Trichoderma for the bioremediation of nickel pollution.

13.
Biology (Basel) ; 10(3)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806264

RESUMO

Three species of the lichen Usnea (U. baileyi (Stirt.) Zahlbr., U. bismolliuscula Zahlbr. and U. pectinata Stirt.) and nine associated endolichenic fungi (ELF) were evaluated using a metabolomics approach. All investigated lichen crude extracts afforded antibacterial activity against Staphylococcus aureus (minimum inhibitory concentration (MIC): 0.0625 mg/mL), but none was observed against Escherichia coli, while the ELF extract Xylaria venustula was found to be the most active against S. aureus (MIC: 2.5 mg/mL) and E. coli (MIC: 5 mg/mL). X. venustula was fractionated and tested for to determine its antibacterial activity. Fractions XvFr1 to 5 displayed bioactivities against both test bacteria. Selected crude extracts and fractions were subjected to metabolomics analyses using high-resolution LC-MS. Multivariate analyses showed the presence of five secondary metabolites unique to bioactive fractions XvFr1 to 3, which were identified as responsible for the antibacterial activity of X. venustula. The p-values of these metabolites were at the margin of significance level, with methyl xylariate C (P_60) being the most significant. However, their high variable importance of projection (VIP) scores (>5) suggest these metabolites are potential diagnostic metabolites for X. venustula for "dual" bioactivity against S. aureus and E. coli. The statistical models also showed the distinctiveness of metabolites produced by lichens and ELF, thus supporting our hypotheses of ELF functionality similar to plant endophytes.

14.
Evol Bioinform Online ; 17: 1176934321989713, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613025

RESUMO

Cycads have developed a complex root system categorized either as normal or coralloid roots. Past literatures revealed that a great diversity of key microbes is associated with these roots. This recent study aims to comprehensively determine the diversity and community structure of bacteria and fungi associated with the roots of two Cycas spp. endemic to China, Cycas debaoensis Zhong & Chen and Cycas fairylakea D.Y. Wang using high-throughput amplicon sequencing of the full-length 16S rRNA (V1-V9 hypervariable) and short fragment ITS region. The total DNA from 12 root samples were extracted, amplified, sequenced, and analyzed. Resulting sequences were clustered into 61 bacteria and 2128 fungal OTUs. Analysis of community structure revealed that the coralloid roots were dominated mostly by the nitrogen-fixer Nostocaceae but also contain other non-diazotrophic bacteria. The sequencing of entire 16S rRNA gene identified four different strains of cyanobacteria under the heterocystous genera Nostoc and Desmonostoc. Meanwhile, the top bacterial families in normal roots were Xanthobacteraceae, Burkholderiaceae, and Bacillaceae. Moreover, a diverse fungal community was also found in the roots of cycads and the predominating families were Ophiocordycipitaceae, Nectriaceae, Bionectriaceae, and Trichocomaceae. Our results demonstrated that bacterial diversity in normal roots of C. fairylakea is higher in richness and abundance than C. debaoensis. On the other hand, a slight difference, albeit insignificant, was noted for the diversity of fungi among root types and host species as the number of shared taxa is relatively high (67%). Our results suggested that diverse microbes are present in roots of cycads which potentially interact together to support cycads survival. Our study provided additional knowledge on the microbial diversity and composition in cycads and thus expanding our current knowledge on cycad-microbe association. Our study also considered the possible impact of ex situ conservation on cyanobiont community of cycads.

15.
ISME J ; 15(2): 618-621, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33005005

RESUMO

Soil bacteria and fungi are key drivers of carbon released from soils to the atmosphere through decomposition of plant-derived organic carbon sources. This process has important consequences for the global climate. While global change factors, such as increased temperature, are known to affect bacterial- and fungal-mediated decomposition rates, the role of trophic interactions in affecting decomposition remains largely unknown. We designed synthetic microbial communities consisting of eight bacterial and eight fungal species and tested the influence of predation by a model protist, Physarum polycephalum, on litter breakdown at 17 and 21 °C. Protists increased CO2 release and litter mass loss by ~35% at 17 °C lower temperatures, while they only had minor effects on microbial-driven CO2 release and mass loss at 21 °C. We found species-specific differences in predator-prey interactions, which may affect microbial community composition and functioning and thus underlie the impact of protists on litter breakdown. Our findings suggest that microbial predation by fast-growing protists is of under-appreciated functional importance, as it affects decomposition and, as such, may influence global carbon dynamics. Our results indicate that we need to better understand the role of trophic interactions within the microbiome in controlling decomposition processes and carbon cycling.


Assuntos
Ciclo do Carbono , Fungos , Animais , Carbono , Ecossistema , Solo , Microbiologia do Solo , Temperatura
16.
3 Biotech ; 10(5): 212, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32351870

RESUMO

A total of nine endolichenic fungi were isolated from the foliose lichen Parmotrema rampoddense (Nyl.) Hale. Of the nine endolichenic fungi, three taxa (Fusarium proliferatum, Nemania primolutea, Daldinia eschsholtzii) showed antibacterial activities as determined by the disk diffusion assay against ESKAPE bacterial pathogens. Fusarium proliferatum gave the most active fungal extract with zone of inhibition values of 15 mm and 19 mm against E. faecalis and S. aureus, respectively. Further chromatographic purification of the F. proliferatum ethyl acetate extract led to the isolation and identification of bis(2-ethylhexyl)terephthalate (1), acetyl tributyl citrate (2), and fusarubin (3). Acetyl tributyl citrate (2) exhibited moderate antibacterial activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.

17.
Int J Pharm ; 566: 500-512, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31129341

RESUMO

We present here the development of a photochemical model used to quantify the risk to photodegradation of a solid drug substance. A key feature of the proposed model development is streamlined estimation of the dependence of the absorption spectra and the quantum yield to the wavelength. A mathematical description of the relationship between the quantum yield and the wavelength enables estimation of photodegradation kinetics under any light anticipated to be encountered in the manufacturing environment. The system studied here consisted of a first order irreversible transformation (A → B(1Φ)) and the formalism strongly suggested the quantum yield was constant over the relevant wavelength range. The predictive power of the model enabled the design of a control strategy to limit the formation of the photo-degradant to very low levels. Also presented are insights obtained from quantum mechanical modeling of the electronic transitions associated with the UV absorption spectra.


Assuntos
Modelos Teóricos , Preparações Farmacêuticas/efeitos da radiação , Fotólise , Estabilidade de Medicamentos , Cinética , Luz , Espectrofotometria Ultravioleta
18.
J Org Chem ; 83(18): 11133-11144, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30102035

RESUMO

Two efficient asymmetric routes to γ-secretase modulator BMS-932481, under investigation for Alzheimer's disease, have been developed. The key step for the first route involves a challenging enantioselective hydrogenation of an unfunctionalized trisubstituted alkene to establish the benzylic stereocenter, representing a very rare case of achieving high selectivity on a complex substrate. The second route demonstrates the first example of a vinylogous dynamic kinetic resolution (VDKR) ketone reduction, where the carbonyl and the racemizable stereocenter are not contiguous, but are conjugated through a pyrimidine ring. Not only did this transformation require both catalyst and substrate control to correctly establish the two stereocenters, but it also necessitated that the nonadjacent benzylic center of the ketone substrate be more acidic than that of the alcohol product to make the process dynamic. DFT computations aided the design of this novel VDKR pathway by reliably predicting the relative acidities of the intermediates involved.


Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Compostos de Anilina/química , Compostos de Anilina/síntese química , Pirimidinas/química , Pirimidinas/síntese química , Compostos de Anilina/farmacologia , Catálise , Técnicas de Química Sintética , Ciclização , Teoria da Densidade Funcional , Hidrogenação , Cetonas/química , Cinética , Oxirredução , Pirimidinas/farmacologia , Estereoisomerismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-29904513

RESUMO

The use of graphical illustration in lecture presentations can make a seemingly boring lesson more attractive and enticing to students. Creating science-themed illustrations and science-based narratives can also lead to creative and critical thinking among students. We used writing editorials and creating editorial cartoons as a learning activity to promote critical thinking and creative skills that are essential in communicating scientific information. This activity can be used with a range of audiences, at various educational levels and in basic to advanced courses.

20.
Eur J Pharm Biopharm ; 120: 63-72, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28834735

RESUMO

Photochemical kinetic models to describe the solution phase degradation of pharmaceutical compounds have been extensively reported, but formalisms applicable to the solid phase under polychromatic light have not received as much attention. The objective of this study was to develop a mathematical model to describe the solid state photodegradation of pharmaceutical powder materials under different area/volumetric scales and light exposure conditions. The model considered the previous formalism presented for photodegradation kinetics in solution phase with important elements applied to static powder material being irradiated with a polychromatic light source. The model also included the influence of optical phenomena (i.e. reflectance, scattering factors, etc.) by applying Beer-Lambert law to light attenuation, including effects of powder density. Drug substance and drug product intermediates (blends and tablet cores) were exposed to different light sources and intensities. The model reasonably predicted the photodegradation levels of powder beds of drug substance and drug product intermediates under white and yellow lights with intensities around 5-11kLux. Importantly, the model estimates demonstrated that the reciprocity law for photoreactions was held. Further model evaluation showed that, due to light attenuation, the powder bed is in virtual darkness at cake depths greater than 500µm. At 100µm, the photodegradation of the investigated compound is expected to be close to 100% in 10days under white fluorescent halophosphate light at 9.5kLux. For tablets, defining the volume over exposed surface area ratio is more challenging. Nevertheless, the model can consider a bracket between worst and best cases to provide a reasonable photodegradation estimate. This tool can be significantly leveraged to simulate different light exposure scenarios while assessing photostability risk in order to define appropriate control strategy in manufacturing.


Assuntos
Pós/química , Comprimidos/química , Estabilidade de Medicamentos , Corantes Fluorescentes/química , Cinética , Luz , Modelos Teóricos , Fotólise/efeitos dos fármacos , Soluções/química
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