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Ensuring Access to Safe and Nutritious Food for All Through the Transformation of Food Systems
Norsk rå kumelk, en kilde til zoonotiske patogener?
The worldwide emerging trend of eating “natural” foods, that has not been
processed, also applies for beverages. According to Norwegian legislation, all
milk must be pasteurized before commercial sale but drinking milk that has
not been heat-treated, is gaining increasing popularity. Scientist are warning
against this trend and highlights the risk of contracting disease from milkborne
microorganisms. To examine potential risks associated with drinking
unpasteurized milk in Norway, milk- and environmental samples were
collected from dairy farms located in south-east of Norway. The samples
were analyzed for the presence of specific zoonotic pathogens; Listeria
monocytogenes, Campylobacter spp., and Shiga toxin-producing Escherichia
coli (STEC). Cattle are known to be healthy carriers of these pathogens, and
Campylobacter spp. and STEC have a low infectious dose, meaning that
infection can be established by ingesting a low number of bacterial cells. L.
monocytogenes causes one of the most severe foodborne zoonotic diseases,
listeriosis, that has a high fatality rate. All three pathogens have caused milk
borne disease outbreaks all over the world, also in Norway.
During this work, we observed that the prevalence of the three examined
bacteria were high in the environment at the examined farms. In addition, 7%
of the milk filters were contaminated by STEC, 13% by L. monocytogenes and
4% by Campylobacter spp. Four of the STEC isolates detected were eaepositive,
which is associated with the capability to cause severe human
disease. One of the eae-positive STEC isolates were collected from a milk
filter, which strongly indicate that Norwegian raw milk may contain potential
pathogenic STEC.
To further assess the possibilities of getting ill by STEC after consuming raw
milk, we examined the growth of the four eae-positive STEC isolates in raw milk at different temperatures. All four isolates seemed to have ability to multiply in raw milk at 8°C, and one isolate had significant growth after 72 hours. Incubation at 6°C seemed to reduce the number of bacteria during the
first 24 hours before cell death stopped. These findings highlight the
importance of stable refrigerator temperatures, preferable < 4°C, for storage
of raw milk.
The L. monocytogenes isolates collected during this study show genetic
similarities to isolates collected from urban and rural environmental
locations, but different clones were predominant in agricultural
environments compared to clinical and food environments. However, the
results indicate that the same clone can persist in a farm over time, and that
milk can be contaminated by L. monocytogenes clones present in farm
environment.
Despite testing small volumes (25 mL) of milk, we were able to isolate both
STEC and Campylobacter spp. directly from raw milk. A proportion of 3% of
the bulk tank milk and teat milk samples were contaminated by
Campylobacter spp. and one STEC was isolated from bulk tank milk. L
monocytogenes was not detected in bulk tank milk, nor in teat milk samples.
The agricultural evolvement during the past decades have led to larger
production units and new food safety challenges. Dairy cattle production in
Norway is in a current transition from tie-stall housing with conventional
pipeline milking systems, to modern loose housing systems with robotic
milking. The occurrence of the three pathogens in this project were higher in
samples collected from farms with loose housing compared to those with tiestall
housing.
Pasteurization of cow’s milk is a risk reducing procedure to protect
consumers from microbial pathogens and in most EU countries, commercial
distribution of unpasteurized milk is legally restricted. Together, the results
presented in this thesis show that the animal housing may influence the level
of pathogenic bacteria in the raw milk and that ingestion of Norwegian raw
cow’s milk may expose consumers to pathogenic bacteria which can cause
severe disease, especially in children, elderly and in persons with underlying
diseases. The results also highlight the importance of storing raw milk at low
temperatures between milking and consumption.Å spise mat som er mindre prosessert og mer «naturlig» er en pågående
trend i Norge og i andre deler av verden. Interessen for å drikke melk som
ikke er varmebehandlet, såkalt rå melk, er også økende. I Norge er det påbudt
å pasteurisere melk før kommersielt salg for å beskytte forbrukeren mot
sykdomsfremkallende mikroorganismer. Fagfolk advarer mot å drikke rå
melk, og påpeker risikoen for å bli syk av patogene bakterier som kan finnes i
melken.
I denne avhandlingen undersøker vi den potensielle risikoen det medfører å
drikke upasteurisert melk fra Norge. I tillegg til å samle inn tankmelk- og
speneprøver fra melkegårder i sørøst Norge, samlet vi også miljøprøver fra
de samme gårdene for å kartlegge forekomst og for å identifisere potensielle
mattrygghetsrisikoer i melkeproduksjonen. Alle prøvene ble analysert for de
zoonotiske sykdomsfremkallende bakteriene Listeria monocytogenes,
Campylobacter spp., og Shiga toksin-produserende Escherichia coli (STEC).
Kyr kan være friske smittebærere av disse bakteriene, som dermed kan
etablere et reservoar på gårdene. Bakteriene kan overføres fra gårdsmiljøet
til melkekjeden og dermed utfordre mattryggheten. Disse bakteriene har
forårsaket melkebårne sykdomsutbrudd over hele verden, også i Norge.
Campylobacter spp. og STEC har lav infeksiøs dose, som vil si at man kan bli
syk selv om man bare inntar et lavt antall bakterieceller. L. monocytogenes
kan gi sykdommen listeriose, en av de mest alvorlige matbårne zoonotiske
sykdommene vi har i den vestlige verden.
Resultater fra denne oppgaven viser en høy forekomst av de tre patogenene i
gårdsmiljøet. I tillegg var 7% av melkefiltrene vi testet positive for STEC, 13%
positive for L. monocytogenes og 4% positive for Campylobacter spp.. Fire av
STEC isolatene bar genet for Intimin, eae, som er ansett som en viktig
virulensfaktor som øker sjansen for alvorlig sykdom. Ett av de eae-positive
isolatene ble funnet i et melkefilter, noe som indikerer at norsk rå melk kan
inneholde patogene STEC. For å videre vurdere risikoen for å bli syk av STEC
fra rå melk undersøkte vi hvordan de fire eae-positive isolatene vokste i rå
melk lagret ved forskjellige temperaturer. For alle isolatene økte antall
bakterier etter lagring ved 8°C, og for et isolat var veksten signifikant. Etter
lagring ved 6°C ble antallet bakterier redusert de første 24 timene, deretter
stoppet reduksjonen i antall bakterier. Disse resultatene viser hvor viktig det
er å ha stabil lav lagringstemperatur for rå melk, helst < 4°C.
L. monocytogenes isolatene som ble samlet inn fra melkegårdene viste
genetiske likheter med isolater samlet inn fra urbane og rurale miljøer rundt
omkring i Norge. Derimot var kloner som dominerte i landbruksmiljøet
forskjellige fra kliniske isolater og isolater fra matproduksjonslokaler. Videre
så man at en klone kan persistere på en gård over tid og at melk kan
kontamineres av L. monocytogenes kloner som er til stede i gårdsmiljøet.
Til tross for små testvolum av tankmelken (25 mL) fant vi både STEC og
Campylobacter spp. i melkeprøvene. 3% av tankmelkprøvene og
speneprøvene var positive for Campylobacter spp. og ett STEC isolat ble
funnet i tankmelk. L. monocytogenes ble ikke funnet direkte i melkeprøvene.
Landbruket i Norge er i stadig utvikling der besetningene blir større, men
færre. Melkebesetningene er midt i en overgang der tradisjonell oppstalling
med melking på bås byttes ut med løsdriftssystemer og melkeroboter.
Forekomsten av de tre patogenene funnet i denne studien var høyere i
besetningene med løsdrift sammenliknet med besetningene som hadde
melkekyrne oppstallet på bås.
Pasteurisering er et viktig forebyggende tiltak for å beskytte konsumenter fra
mikrobielle patogener, og i de fleste EU-land er kommersielt salg av rå melk
juridisk begrenset. Denne studien viser at oppstallingstype kan påvirke
nivåene av patogene bakterier i gårdsmiljøet og i rå melk. Inntak av rå melk
kan eksponere forbruker for patogene bakterier som kan gi alvorlig sykdom,
spesielt hos barn, eldre og personer med underliggende sykdommer.
Resultatene underbygger viktigheten av å pasteurisere melk for å sikre
mattryggheten, og at det er avgjørende å lagre rå melk ved kontinuerlig lave
temperaturer for å forebygge vekst av zoonotiske patogener
Anuário científico da Escola Superior de Tecnologia da Saúde de Lisboa - 2021
É com grande prazer que apresentamos a mais recente edição (a 11.ª) do Anuário Científico da Escola Superior de Tecnologia da Saúde de Lisboa. Como instituição de ensino superior, temos o compromisso de promover e incentivar a pesquisa científica em todas as áreas do conhecimento que contemplam a nossa missão. Esta publicação tem como objetivo divulgar toda a produção científica desenvolvida pelos Professores, Investigadores, Estudantes e Pessoal não Docente da ESTeSL durante 2021. Este Anuário é, assim, o reflexo do trabalho árduo e dedicado da nossa comunidade, que se empenhou na produção de conteúdo científico de elevada qualidade e partilhada com a Sociedade na forma de livros, capítulos de livros, artigos publicados em revistas nacionais e internacionais, resumos de comunicações orais e pósteres, bem como resultado dos trabalhos de 1º e 2º ciclo. Com isto, o conteúdo desta publicação abrange uma ampla variedade de tópicos, desde temas mais fundamentais até estudos de aplicação prática em contextos específicos de Saúde, refletindo desta forma a pluralidade e diversidade de áreas que definem, e tornam única, a ESTeSL. Acreditamos que a investigação e pesquisa científica é um eixo fundamental para o desenvolvimento da sociedade e é por isso que incentivamos os nossos estudantes a envolverem-se em atividades de pesquisa e prática baseada na evidência desde o início dos seus estudos na ESTeSL. Esta publicação é um exemplo do sucesso desses esforços, sendo a maior de sempre, o que faz com que estejamos muito orgulhosos em partilhar os resultados e descobertas dos nossos investigadores com a comunidade científica e o público em geral. Esperamos que este Anuário inspire e motive outros estudantes, profissionais de saúde, professores e outros colaboradores a continuarem a explorar novas ideias e contribuir para o avanço da ciência e da tecnologia no corpo de conhecimento próprio das áreas que compõe a ESTeSL. Agradecemos a todos os envolvidos na produção deste anuário e desejamos uma leitura inspiradora e agradável.info:eu-repo/semantics/publishedVersio
Machine Learning Research Trends in Africa: A 30 Years Overview with Bibliometric Analysis Review
In this paper, a critical bibliometric analysis study is conducted, coupled
with an extensive literature survey on recent developments and associated
applications in machine learning research with a perspective on Africa. The
presented bibliometric analysis study consists of 2761 machine learning-related
documents, of which 98% were articles with at least 482 citations published in
903 journals during the past 30 years. Furthermore, the collated documents were
retrieved from the Science Citation Index EXPANDED, comprising research
publications from 54 African countries between 1993 and 2021. The bibliometric
study shows the visualization of the current landscape and future trends in
machine learning research and its application to facilitate future
collaborative research and knowledge exchange among authors from different
research institutions scattered across the African continent
Mathematical models to evaluate the impact of increasing serotype coverage in pneumococcal conjugate vaccines
Of over 100 serotypes of Streptococcus pneumoniae, only 7 were included in the first pneumo- coccal conjugate vaccine (PCV). While PCV reduced the disease incidence, in part because of a herd immunity effect, a replacement effect was observed whereby disease was increasingly caused by serotypes not included in the vaccine. Dynamic transmission models can account for these effects to describe post-vaccination scenarios, whereas economic evaluations can enable decision-makers to compare vaccines of increasing valency for implementation. This thesis has four aims. First, to explore the limitations and assumptions of published pneu- mococcal models and the implications for future vaccine formulation and policy. Second, to conduct a trend analysis assembling all the available evidence for serotype replacement in Europe, North America and Australia to characterise invasive pneumococcal disease (IPD) caused by vaccine-type (VT) and non-vaccine-types (NVT) serotypes. The motivation behind this is to assess the patterns of relative abundance in IPD cases pre- and post-vaccination, to examine country-level differences in relation to the vaccines employed over time since introduction, and to assess the growth of the replacement serotypes in comparison with the serotypes targeted by the vaccine. The third aim is to use a Bayesian framework to estimate serotype-specific invasiveness, i.e. the rate of invasive disease given carriage. This is useful for dynamic transmission modelling, as transmission is through carriage but a majority of serotype-specific pneumococcal data lies in active disease surveillance. This is also helpful to address whether serotype replacement reflects serotypes that are more invasive or whether serotypes in a specific location are equally more invasive than in other locations. Finally, the last aim of this thesis is to estimate the epidemiological and economic impact of increas- ing serotype coverage in PCVs using a dynamic transmission model. Together, the results highlight that though there are key parameter uncertainties that merit further exploration, divergence in serotype replacement and inconsistencies in invasiveness on a country-level may make a universal PCV suboptimal.Open Acces
Detection of covid 19 from an imbalanced chest x-ray image data set
The Covid-19 pandemic has spread quickly, making identification
of the virus critically important in assisting overburdened healthcare
systems. Numerous techniques have been used to identify Covid-19,
of which the Polymerase chain reaction (PCR) test is the most common.
However, obtaining results from the PCR test can take up to two days.
An alternative is to use X-ray images of the subject’s chest area as inputs
to a deep learning neural networks algorithm. The two problems
with this approach are the choice of architecture and the method used
to deal with the imbalanced data. In this study a comparative analysis of
a standard convolutional neural network (CNN) and a number of transfer
learning algorithms with a range of imbalanced data techniques was
conducted to detect Covid-19 from a data set of chest x-ray images. This
data set was an amalgamation of two data sets extracted from the Kaggle
Covid-19 open source data repository and non-Covid illnesses taken
from the National Institute of Health. The resulting data set was had
over 115k records and 15 different type of findings ranging from no-illness
to illnesses such as Covid-19, emphysema and lung cancer. This study
addresses the problem of class imbalance on the largest data set used
for x-ray detection of Covid-19 by combining undersampling and oversampling
methods. The results showed that a CNN model in conjunction
with these random over and under sampling methods outperformed all
other candidates when identifying Covid-19 with a F1-score of 93%, a
precision of 90% and a recall of 91%
A correlation between tellurite resistance and nitric oxide detoxification in Salmonella Typhimurium
Salmonella are important enteric pathogens that are responsible for causing various diseases from gastroenteritis to systemic typhoid fever. Salmonella are a major contributor to morbidity and mortality worldwide. Crucial to their pathogenesis is the survival in harmful conditions elicited by the host immune system, one of these being reactive oxygen and nitrogen species (ROS/RNS). These are produced by macrophages and neutrophils in an attempt to eliminate pathogens. Salmonella, have the unique ability to colonise macrophages and have dedicated nitric oxide (NO) detoxification systems. There are three prominent metalloenzymes (HmpA, NorVW and NrfA) heavily researched in the literature for NO detoxification. Previous work suggested that more proteins are responsible for the nitrosative stress response with these being regulated by the nitric oxide sensitive transcriptional repressor, NsrR.
This study demonstrates a relationship between three putative tellurite resistance proteins regulated by NsrR (STM1808, YeaR and TehB) and NO detoxification. A Functional redundancy between these proteins was observed for anaerobic protection against NO and tellurite. Furthermore, this study identified that proteins responsible in NO protection such as HmpA and YtfE also provide resistance to tellurite during aerobic and anaerobic conditions, respectively. Tellurite resistant Salmonella strains were evolved by continued passage in this study that consequently had altered H2O2 resistance profiles and increased sensitivity to antibiotics. However, these strains were not significantly attenuated during macrophage survival or during the presence of NO in vitro. Additionally, the hypothetical protein YgbA, which has predicted roles in NO detoxification, was found to be important to Salmonella survival in macrophages. However, in vitro NO exposure with the NO donor deta NONOate only showed a role for anaerobic protection
A Molecular Approach to the Diagnosis, Assessment, Monitoring and Treatment of Pulmonary Non-Tuberculous Mycobacterial Disease
Introduction: Non-Tuberculous Mycobacteria (NTM) can cause disease of the lungs and sinuses, lymph nodes, joints and central nervous system as well as disseminated infections in immunocompromised individuals. Efforts to tackle infections in NTM are hampered by a lack of reliable biomarkers for diagnosis, assessment of disease activity, and prognostication.
Aims: The broad aims of this thesis are:
1. to develop molecular assays capable of quantifying the 6 most common pathogenic mycobacteria (M. abscessus, M. avium, M. intracellulare, M. malmoense, M. kansasii, M. xenopi) and calculate comparative sensitivities and specificities for each assay.
2. to assess patients’ clinical course over 12 – 18 months by performing the developed molecular assays against DNA extracted from sputum from patients with NTM infection.
3. to assess dynamic bacterial changes of the lung microbiome in patients on treatment for NTM disease and those who are treatment na ve.
Methods: DNA was extracted from a total of 410 sputum samples obtained from 38 patients who were either:
• commencing treatment for either M. abscessus or Mycobacterium avium complex.
• considered colonised with M. abscessus or Mycobacterium avium complex (i.e. cultured NTM but were not deemed to have infection as they did not meet ATS or BTS criteria for disease).
• Diagnosed with cystic fibrosis (CF) or non-CF bronchiectasis but had never cultured NTM.
For the development of quantitative molecular assays, NTM hsp65 gene sequences were aligned and interrogated for areas of variability. These variable regions enabled the creation of species specific probes. In vitro sensitivity and specificity for each probe was determined by testing each probe against a panel of plasmids containing hsp65
gene inserts from different NTM species. Quantification accuracy was determined by using each assay against a mock community containing serial dilutions of target DNA.
Each sample was tested with the probes targeting: M. abscessus, M. avium and M. intracellulare producing a longitudinal assessment of NTM copy number during each patient’s clinical course.
In addition, a total of 64 samples from 16 patients underwent 16S rRNA gene sequencing to characterise longitudinal changes in the microbiome of both NTM disease and controls.
Results: In vitro sensitivity for the custom assays were 100% and specificity ranged from 91.6% to 100%. In terms of quantification accuracy, there was no significant difference between the measured results of each assay and the expected values when performed in singleplex. The assays were able to accurately determine NTM copy number to a theoretical limit of 10 copies/μl.
When used against samples derived from human sputum and using culture results as a gold standard, the sensitivity of the assay for M. abscessus was found to be 0.87 and 0.86 for MAC. The specificity of the assay for M. abscessus was 0.95 and 0.62 for MAC. The negative predictive value of the assay for M. abscessus was 0.98 and 0.95 for MAC. This resulted in an AUC of 0.92 for M. abscessus and 0.74 for MAC.
Longitudinal analysis of the lung microbiome using 16SrRNA gene sequencing showed that bacterial burden initially decreases after initiation of antibiotic therapy but begins to return to normal levels over several months of antibiotic therapy. This effect is mirrored by changes in alpha diversity. The decrease in bacterial burden and loss of alpha diversity was found to be secondary to significant changes in specific genera such as Veillonella and Streptococcus. The abundance of other Proteobacteria such as Pseudomonas remain relatively constant.
Conclusion: The molecular assay has shown high in vitro sensitivity and specificity for the detection and accurate quantification of the 6 most commonly pathogenic NTM species. The assays successfully identified NTM DNA from human sputum samples.
A notable association between NTM copy number and the cessation of one or more antibiotics existed (i.e. when one antibiotic was stopped because of patient intolerance, NTM copy number increased, often having been unrecordable prior to this). The qPCR assays developed in this thesis provide an affordable, real time and rapid measurement of NTM burden allowing clinicians to act on problematic results sooner than currently possible.
There was no significant difference between the microbiome in bronchiectasis and cystic fibrosis nor was there a significant difference between the microbiome in patients requiring treatment for NTM and those who did not. Patients receiving treatment experienced an initial decrease in bacterial burden over the first weeks of treatment followed by a gradual increase towards baseline over the next weeks to months. This change was mirrored in measures of alpha diversity. Changes in abundance and diversity were accounted for by decreases in specific bacteria whilst the abundance of other bacteria increased, occupying the microbial niche created. These bacteria (for example Pseudomonas spp) are often associated with morbidity.Open Acces
Repurposing based identification of novel inhibitors against mmps5-mmpl5 efflux pump of Mycobacterium smegmatis: A combined in silico and in vitro study
In the current era of a pandemic, infections of COVID-19 and Tuberculosis (TB) enhance
the detrimental effects of both diseases in suffering individuals. The resistance mechanisms evolving
in Mycobacterium tuberculosis are limiting the efficiency of current therapeutic measures and pressurizing
the stressed medical infrastructures. The bacterial efflux pumps enable the development
of resistance against recently approved drugs such as bedaquiline and clofazimine. Consequently,
the MmpS5-MmpL5 protein system was selected because of its role in efflux pumping of anti-TB
drugs. The MmpS5-MmpL5 systems of Mycobacterium smegmatis were modelled and the virtual
screening was performed using an ASINEX library of 5968 anti-bacterial compounds. The inhibitors
with the highest binding affinities and QSAR based highest predicted inhibitory concentration were
selected. The MmpS5-MmpL5 associated systems with BDE_26593610 and BDD_27860195 showed
highest inhibitory parameters
Estudos das superfícies de Hirshfeld, docking molecular e análise de parâmetros farmacocinéticos de ADME de complexos de Níquel(II) com tiossemicarbazonas
Thiosemicarbazones (TSCs) are compounds that have diverse biological and pharmacological applications. Previous biological studies involving the antibacterial activity of Co(III), Cu(II) and Mn(II) complexes derived from TSCs revealed complexes with promising biological potential. Thus, the present study aimed to evaluate the theoretical antibacterial activity of Ni(II) complexes containing TSCs against five bacterial cultures (S. mutans, S. mitis, S. sanguinis, L. paracasei and E. faecalis) through of molecular docking and to analyze in silico the pharmacokinetic parameters of ADME. For these experiments two different types of Ni(II) complexes with tridentate ligands of the type 2-acetylpyridine-N(4)-R-thiosemicarbazone (Hatc-R) were used. The R group of the Hatc-R ligand was replaced by ethyl (Et, 1) and phenyl (Ph, 2), to form [Ni(atc-Et)2, 3] and [Ni(atc-Ph)2, 4] complexes. The analysis of the Hirshfeld surface of the complex 3 revealed that the supramolecular structure is stabilized by interactions of the type H···H, C···H/H···C, N··· H/H···N and S···H/H···S. Molecular docking studies of the free ligands 1 and 2 and metal complexes 3 and 4 were performed with the crystalline structures of the enzymes of the bacteria mentioned above and the results showed highly exergonic ΔG values that reveal good orientation and binding affinity. The complex 4 showed the best results among all compounds tested. The ΔG values for the 4 complex were –10.09 kcal mol–1 for L. paracasei, followed by –8.95 kcal mol–1 for S. mutans while the best value of ΔG of the 3 complex was –7.24 kcal mol–1 for L. paracasei. The results of the in silico study of ADME for 1, 2, 3 and 4 showed that these compounds are in accordance with the rules of Lipinski, Ghose, Veber and Egan, in addition to having good solubility and characteristics suitable for oral use. The compounds were also evaluated for human intestinal absorption (HIA), blood-brain barrier (BBB) penetration, inhibition of isoenzymes belonging to the CYP450 system and none of the compounds are able to cross the blood-brain barrier and inhibit CYP2D6 and CYP3A4 isoenzymes belonging to the CYP450 system. Thus, this study demonstrates that the compounds have a promising pharmacokinetic profile aiming their therapeutic application through antibacterial activity.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorTrabalho de Conclusão de Curso (Graduação)Tiossemicarbazonas (TSCs) são compostos que possuem diversas aplicações biológicas e farmacológicas. Estudos biológicos anteriores envolvendo a atividade antibacteriana de complexos de Co(III), Cu(II) e Mn(II) derivados de TSCs revelaram complexos com potencial biológico promissor. Assim, o presente estudo teve como objetivo avaliar a atividade antibacteriana teórica de complexos de Ni(II) contendo TSCs frente a cinco culturas bacterianas (S. mutans, S. mitis, S. sanguinis, L. paracasei e E. faecalis) por meio do docking molecular e analisar in silico os parâmetros farmacocinéticos de ADME. Para estes experimentos dois tipos diferentes de complexos de Ni(II) com ligantes tridentados do tipo 2-acetilpiridina-N(4)-R-tiossemicarbazona (Hatc-R) foram usados. O grupo R do ligante Hatc-R foi substituído por etil (Et, 1) e fenil (Ph, 2), para formar complexos do tipo [Ni(atc-Et)2, 3] e [Ni(atc-Ph)2, 4]. A análise da superfície de Hirshfeld do complexo 3 revelou que a estrutura supramolecular é estabilizada por interações do tipo H···H, C···H/H···C, N···H/H···N e S···H/H···S. Os estudos de docking molecular dos ligantes livres 1 e 2 e complexos metálicos 3 e 4 foram realizados com as estruturas cristalinas das enzimas das bactérias mencionadas acima e os resultados mostraram valores de ΔG altamente exergônico que revelam boa orientação e afinidade de ligação. O complexo 4 apresentou os melhores resultados entre todos os compostos testados. Os valores de ΔG para o complexo 4 foram de –10,09 kcal mol–1 para L. paracasei, seguida por –8,95 kcal mol–1 para S. mutans enquanto o melhor valor de ΔG do complexo 3 foi de –7,24 kcal mol–1 para L. paracasei. Os resultados do estudo in silico de ADME para 1, 2, 3 e 4 mostraram que estes compostos estão de acordo com as regras de Lipinski, Ghose, Veber e Egan, além de apresentarem boa solubilidade e características apropriadas para serem utilizadas por via oral. Os compostos também foram avaliados quanto à absorção intestinal humana (HIA), penetração na barreira hematoencefálica (BBB), inibição das isoenzimas pertencentes ao sistema CYP450 sendo que nenhum dos compostos são capazes de atravessar a barreira hematoencefálica e inibir as isoenzimas CYP2D6 e CYP3A4 pertencentes ao sistema CYP450. Assim, esse estudo demonstra que os compostos apresentam um perfil farmacocinético promissor visando sua aplicação terapêutica através da atividade antibacteriana
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