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1.
Heliyon ; 10(3): e25077, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38327451

RESUMO

The rapid emergence of resistance to existing frontline antimalarial drugs emphasizes a need for the development of target-oriented molecules with novel modes of action. Given the importance of a plant-like Calcium-Dependent Protein Kinase 1 (PfCDPK1) as a stand-alone multistage signalling regulator of P. falciparum, we designed and synthesized 7-chloroquinoline-indole-chalcones tethered with a triazole (CQTrICh-analogs 7 (a-s) and 9) directed towards PfCDPK1. This was accomplished by reacting substituted 1-phenyl-3-(1-(prop-2-yn-1-yl)-1H-indol-3-yl) prop-2-en-1-one and 1-(prop-2-yn-1-yl)-1H-indole-3-carbaldehyde with 4-azido-7-chloroquinoline, respectively via a 'click' reaction. The selected CQTrICh-analogs: 7l and 7r inhibited the growth of chloroquine-sensitive 3D7 strain and -resistant RKL-9 isolate of Plasmodium falciparum, with IC50 values of 2.4 µM & 1.8 µM (7l), and 3.5 µM & 2.7 µM (7r), respectively, and showed no apparent hemolytic activity and cytotoxicity in mammalian cells. Intra-erythrocytic progression studies revealed that the active hybrids: 7l and 7r are effective against the mature stages of the parasite. 7l and 7r were found to stably interact with the catalytically active ATP-binding pocket of PfCDPK1 via energetically favourable H-bonds. The interaction was confirmed in vitro by microscale thermophoresis and kinase assays, which demonstrated that the active hybrids interact with PfCDPK1 and inhibit its kinase activity which is presumably responsible for the parasite growth inhibition. Interestingly, 7l and 7r showed no inhibitory effect on the human kinases, indicating their selectivity for the parasite kinase. We report the antiplasmodial potential of novel kinase-targeting bio-conjugates, a step towards developing pan-kinase inhibitors which is a prerequisite for multistage anti-malarial protection.

2.
ACS Omega ; 9(5): 5576-5591, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38343956

RESUMO

This study was conducted to explore the interaction between two plant-based antiplasmodial compounds, gartanin and friedelin, and bovine serum albumin (BSA). The objectives aimed to elucidate the binding characteristics, structural changes, and thermodynamic parameters associated with the interaction. Various methods were used including UV-vis, fluorescence, and circular dichroism spectroscopy, supported by molecular docking and molecular dynamics simulation. The results showed a concentration-dependent interaction between the antiplasmodial compounds and BSA, revealing changes in protein conformation and stability. The obtained results showed that the plant products bound with BSA through static quenching with moderate binding affinity (104 M-1) with BSA. Thermodynamic parameters and structural transitions calculated from spectroscopic methods revealed that hydrogen bond and van der Waals forces caused the partial conformational alteration in the secondary structure of BSA as the α-helical content decreased with an increase in ß sheets, random coils, and other structures. Computational analysis provided insights into the binding sites and affinities. The study enhances our understanding of the molecular interactions between BSA protein and antiplamodial compounds obtained from plants, supporting the research of choosing, designing, and optimizing molecules for biomedical applications with a focus on selectively targeting their binding sites.

3.
Eur J Med Chem ; 265: 116041, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38199162

RESUMO

The scientific community has shown considerable interest in proteolysis-targeting chimeras (PROTACs) in the last decade, indicating their remarkable potential as a means of achieving targeted protein degradation (TPD). Not only are PROTACs seen as valuable tools in molecular biology but their emergence as a modality for drug discovery has also garnered significant attention. PROTACs bind to E3 ligases and target proteins through respective ligands connected via a linker to induce proteasome-mediated protein degradation. The discovery of small molecule ligands for E3 ligases has led to the prevalent use of various E3 ligases in PROTAC design. Furthermore, the incorporation of different types of linkers has proven beneficial in enhancing the efficacy of PROTACs. By far more than 3300 PROTACs have been reported in the literature. Notably, Von Hippel-Lindau (VHL)-based PROTACs have surfaced as a propitious strategy for targeting proteins, even encompassing those that were previously considered non-druggable. VHL is extensively utilized as an E3 ligase in the advancement of PROTACs owing to its widespread expression in various tissues and well-documented binders. Here, we review the discovery of VHL ligands, the types of linkers employed to develop VHL-based PROTACs, and their subsequent modulation to design advanced non-conventional degraders to target various disease-causing proteins. Furthermore, we provide an overview of other E3 ligases recruited in the field of PROTAC technology.


Assuntos
Quimera de Direcionamento de Proteólise , Ubiquitina-Proteína Ligases , Ubiquitina-Proteína Ligases/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Proteólise , Descoberta de Drogas , Ligantes
4.
PLoS One ; 19(1): e0290306, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38236921

RESUMO

BACKGROUND AND PURPOSE: Management strategies for children with congenital health diseases (CHDs) should encompass more than just the medical aspect of the disease and consider how heart diseases affect their everyday activities and, subsequently, their quality of life (QoL). Global studies witnessed a greater emphasis on studying the QoL associated with CHD. However, there is still a great lag in such data in the Arab region. The purpose of this study was to evaluate QoL in children with CHD using an Arab sample from Jordan. The specific objectives were twofold: (1) to contrast the assessments of children's QoL reported by their parents with those reported by the children themselves, and (2) to assess the factors that influence the QoL of children with CHD. METHODS: A total of 79 children aged 2-18 with a confirmed diagnosis of CHD were included in the study, along with their mothers. Of them, 38.0% were girls, 67.1% were diagnosed with non-cyanotic CHD, 58.2% had a severe CHD, 92.4% had undergone at least one operation, 81.0% had repaired defects, 13.9% underwent palliated procedures, and 24.1% were admitted to a neonatal intensive care unit after delivery. The Pediatric Quality of Life Inventory was used to assess QoL of children with CHD. Both children's and parents' reports of QoL were analyzed using paired-sample t-tests, ANOVAs, and multiple linear regression. RESULTS: Older children reported significantly lower QoL scores, whereas there were no differences in parents-reported QoL scores across different children age groups. There was a divergence in perceptions of QoL between parents-reported and children-reported scores with parents reporting significantly lower scores. The children-reported QoL in this study seemed to be significantly associated with their gender, age, and the presence of learning difficulties, whereas the parent-reported QoL was only associated with the presence of learning difficulties. CONCLUSIONS: Responses from both children and parents need to be considered to understand the similarities and differences between them and to provide further insight into the optimal way to help children with CHD effectively navigate the transition into adulthood. Future research studies of outcomes for survivors of children with CHD are needed to identify high-risk survivors for worse psychosocial functioning and assess prevention measures and treatment interventions to improve their QoL.


Assuntos
Cardiopatias Congênitas , Qualidade de Vida , Criança , Feminino , Recém-Nascido , Humanos , Adolescente , Masculino , Qualidade de Vida/psicologia , Árabes , Cardiopatias Congênitas/psicologia , Análise Multivariada , Modelos Lineares , Pais/psicologia
5.
J Biomol Struct Dyn ; 42(1): 211-230, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36995166

RESUMO

A series of natural alcohols motif containing novel substituted cinnamates were developed and screened against five bacterial strains namely, Enterococcus faecal (E. faecalis), Escherichia coli (E. coli), Bacillus subtilis (B. subtilis), Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumonieae (K. pneumonieae). Among all cinnamates, YS17 was identified with 100% bacterial growth inhibition across the panel, except in E. faecalis with MIC values of 0.25 mg/mL against B. subtilis and P. aeruginosa whereas 0.125, 0.5 and 1 mg/mL against E. coli, K. pneumonieae and E. faecalis, respectively. The growth inhibitory property of YS17 was further validated by disk diffusion, synergistic study and in vitro toxicity assays. Interestingly, YS17 exhibits synergistic effect in combination with the standard drug Ampicillin (AMP). The single crystal structure analysis of YS4 and YS6 was also performed which reconfirmed their proposed structures. Molecular docking visualized significant non-covalent interactions between E. coli MetAP and YS17 and the structural and conformational changes were further analysed using MD simulation studies. Overall, the study provided a suitable core for further synthetic alterations for their optimization as an antibacterial agent. Communicated by Ramaswamy H. Sarma.


Assuntos
Cinamatos , Escherichia coli , Simulação de Acoplamento Molecular , Cinamatos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Pseudomonas aeruginosa , Bacillus subtilis , Etanol , Testes de Sensibilidade Microbiana
6.
Eur J Med Chem ; 264: 115969, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38039787

RESUMO

The persistence of drug resistance poses a significant obstacle to the advancement of efficacious malaria treatments. The remarkable efficacy displayed by 1,2,3-triazole-based compounds against Plasmodium falciparum highlights the potential of triazole conjugates, with diverse pharmacologically active structures, as potential antimalarial agents. We aimed to synthesize 7-dichloroquinoline-triazole conjugates and their structure-activity relationship (SAR) derivatives to investigate their anti-plasmodial activity. Among them, QP11, featuring a m-NO2 substitution, demonstrated efficacy against both chloroquine-sensitive and -resistant parasite strains. QP11 selectively inhibited FP2, a cysteine protease involved in hemoglobin degradation, and showed synergistic effects when combined with chloroquine. Additionally, QP11 hindered hemoglobin degradation and hemozoin formation within the parasite. Metabolic stability studies indicated high stability of QP11, making it a promising antimalarial candidate. In vivo evaluation using a murine malaria model demonstrated QP11's efficacy in eradicating parasite growth without neurotoxicity, presenting it as a promising compound for novel antimalarial development.


Assuntos
Antimaláricos , Malária , Animais , Camundongos , Antimaláricos/química , Piperazina/farmacologia , Triazóis/química , Cloroquina/farmacologia , Malária/tratamento farmacológico , Plasmodium falciparum , Hemoglobinas/metabolismo , Hemoglobinas/farmacologia , Hemoglobinas/uso terapêutico
7.
Surv Ophthalmol ; 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38042377

RESUMO

Retinitis pigmentosa (RP) is often undetected in its early stages. Artificial intelligence (AI) has emerged as a promising tool in medical diagnostics. Therefore, we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of AI in detecting RP using various ophthalmic images. We conducted a systematic search on PubMed, Scopus, and Web of Science databases on December 31, 2022. We included studies in the English language that used any ophthalmic imaging modality, such as OCT or fundus photography, used any AI technologies, had at least an expert in ophthalmology as a reference standard, and proposed an AI algorithm able to distinguish between images with and without retinitis pigmentosa features. We considered the sensitivity, specificity, and area under the curve (AUC) as the main measures of accuracy. We had a total of 14 studies in the qualitative analysis and 10 studies in the quantitative analysis. In total, the studies included in the meta-analysis dealt with 920,162 images. Overall, AI showed an excellent performance in detecting RP with pooled sensitivity and specificity of 0.985 [95%CI: 0.948-0.996], 0.993 [95%CI: 0.982-0.997] respectively. The area under the receiver operating characteristic (AUROC), using a random-effect model, was calculated to be 0.999 [95%CI: 0.998-1.000; P < 0.001]. The Zhou and Dendukuri I² test revealed a low level of heterogeneity between the studies, with [I2 = 19.94%] for sensitivity and [I2 = 21.07%] for specificity. The bivariate I² [20.33%] also suggested a low degree of heterogeneity. We found evidence supporting the accuracy of AI in the detection of RP; however, the level of heterogeneity between the studies was low.

8.
Health Sci Rep ; 6(11): e1668, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37920659

RESUMO

Background and Aims: There is a dearth of information about binge eating disorder (BED) among Bangladeshi university students, who may be more susceptible to BED due to the rise in unhealthy lifestyles and food habits. Therefore, the purpose of this study was to assess the prevalence and associated factors of BED symptoms among Bangladeshi university students. Methods: Students (N = 525) from three public universities in Bangladesh participated in this cross-sectional study between November 2022 and March 2023. Face-to-face interviews were conducted using a structured paper-based questionnaire that included two validated survey tools; the binge eating disorder screener and the patient health questionnaire-9. To identify the factors associated with BED symptoms, multiple logistic regression analysis was conducted, with sociodemographic and behavioral information (e.g., age, sex, smoking status, etc.) considered as covariates. Results: The prevalence of BED symptoms among participants (mean age 21.28 years, 50.3% male and 49.7% female) was 20.6%. Male students had a 2.28 times higher likelihood of having BED symptoms compared to female counterparts (adjusted odds ratio [AOR] = 2.28; 95% CI: 1.33-3.89). Older students (AOR = 3.56, 95% CI: 1.80-7.05), students who were overweight or obese (AOR = 3.32, 95% CI: 1.87-5.89), and students reporting higher depressive symptoms (AOR = 2.69, 95% CI: 1.66-4.35) were at greater risk for developing BED compared to their respective counterparts. Conclusions: This study provides new insights into the prevalence of BED symptoms and its contributing factors among Bangladeshi students. Approximately 1-in-5 university students reported having BED symptoms. University students who are older, overweight, or obese, and who report depressive symptoms may be at greatest risk. Future longitudinal studies are needed to determine the causal factors underlying BED. Findings from this study can assist policymakers and public health professionals in developing effective and targeted strategies to mitigate the risks associated with BED among Bangladeshi university students.

9.
Sci Rep ; 13(1): 16735, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794106

RESUMO

Although secondhand smoke (SHS) exposure is predominant in Bangladesh, the adverse effect of SHS exposure on health-related behaviors, such as sleep quality, have remained an under-investigated area of the country's public health landscape. Therefore, the purpose of this study was to examine the association between SHS exposure and poor sleep quality among non-smoking university students in Bangladesh. A cross-sectional survey was carried out between May and September 2022. SHS exposure (main predictor variable) and other covariates (e.g., age, sex, etc.) were measured using a self-reported questionnaire and sleep quality (outcome variable) was measured via the Pittsburgh Sleep Quality Index. Multiple logistic regression models investigated the association between SHS exposure and poor sleep quality. The study included 390 students (mean age: 22 years, 53.8% male). Approximately 41.8% of the participants reported SHS exposure, and 50.5% had poor sleep quality. Students exposed to SHS were more likely to have poor sleep quality compared to their counterparts (AOR = 1.61; 95% CI 1.01, 2.58). Subgroup analysis revealed poor sleep quality was 2-times higher among male students exposed to SHS than those male students without SHS exposure (AOR = 2.03; 95% CI 1.05, 3.93). No association was found in female students. Findings from this study warrant increased awareness and public health initiatives on the implications of SHS on health behaviors, such as sleep quality, in non-smoking Bangladeshi university students.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Poluição por Fumaça de Tabaco , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Estudos Transversais , Universidades , Bangladesh/epidemiologia , Qualidade do Sono , Inquéritos e Questionários , Autorrelato , Estudantes , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Exposição Ambiental/análise
10.
J Cell Biochem ; 124(9): 1223-1240, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37661636

RESUMO

Microtubule affinity-regulating kinase 4 (MARK4) is a member of the Ser/Thr protein kinase family, phosphorylates the microtubule-connected proteins and plays a vital role in causing cancers and neurodegenerative diseases. This kinase modulates multiple signaling pathways, including mammalian target of rapamycin, nuclear factor-κB, and Hippo-signaling, presumably responsible for cancer and Alzheimer's. MARK4 acts as a negative controller of the Hippo-kinase cassette for promoting YAP/TAZ action, and the loss of MARK4 detains the tumorigenic properties of cancer cells. MARK4 is involved in tau hyperphosphorylation that consequently affects neurodegeneration. MARK4 is a promising drug target for cancer, diabetes, and Alzheimer's. Developing the potent and selective inhibitors of MAKR4 are promising in the therapeutic management of associated diseases. Despite its great significance, a few reviews are available to discuss its structure, function and clinical significance. In the current review, we aimed to provide detailed information on the structural features of MARK4 targeted in drug development and its role in various signaling pathways related to cancer and neurodegenerative diseases. We further described the therapeutic potential of MARK4 inhibitors in preventing numerous diseases. Finally, the updated information on MARK4 will be helpful in the further development of effective therapeutic molecules.


Assuntos
Doença de Alzheimer , Neoplasias , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Neoplasias/tratamento farmacológico , Carcinogênese , Proteínas dos Microtúbulos , Microtúbulos
11.
Luminescence ; 38(12): 2018-2033, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37654050

RESUMO

This study performed a comparative investigation to explore the interaction mechanisms between two potential antimalarial compounds, JMI 346 and JMI 105, and human serum albumin (HSA), a vital carrier protein responsible for maintaining important biological functions. Our aim was to assess the pharmacological efficiency of these compounds while comprehensively analyzing their impact on the dynamic behavior and overall stability of the protein. A comprehensive array of multispectroscopic techniques, including UV-Vis. spectroscopy, steady-state fluorescence analysis, synchronous fluorescence spectroscopy, three-dimensional fluorescence and circular dichroism spectroscopy, docking studies, and molecular dynamics simulations, were performed to probe the intricate details of the interaction between the compounds and HSA. Our results revealed that both JMI 346 and JMI 105 exhibited promising pharmacological effectiveness within the context of malaria therapy. However, JMI 346 was found to exhibit a significantly higher affinity and only minor altered impact on HSA, suggesting a more favorable interaction with the protein on the dynamic behavior and overall stability of the protein in comparison to JMI 105. Further studies can build on these results to optimize the drug-protein interaction and enable the development of more potent and targeted antimalarial treatments.


Assuntos
Antimaláricos , Albumina Sérica Humana , Humanos , Albumina Sérica Humana/química , Antimaláricos/farmacologia , Antimaláricos/química , Ligação Proteica , Dicroísmo Circular , Simulação de Acoplamento Molecular , Espectrometria de Fluorescência/métodos , Termodinâmica , Sítios de Ligação
12.
Microorganisms ; 11(8)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37630494

RESUMO

Biofilms are complex communities of microorganisms that grow on surfaces and are embedded in a matrix of extracellular polymeric substances. These are prevalent in various natural and man-made environments, ranging from industrial settings to medical devices, where they can have both positive and negative impacts. This review explores the diverse applications of microbial biofilms, their clinical consequences, and alternative therapies targeting these resilient structures. We have discussed beneficial applications of microbial biofilms, including their role in wastewater treatment, bioremediation, food industries, agriculture, and biotechnology. Additionally, we have highlighted the mechanisms of biofilm formation and clinical consequences of biofilms in the context of human health. We have also focused on the association of biofilms with antibiotic resistance, chronic infections, and medical device-related infections. To overcome these challenges, alternative therapeutic strategies are explored. The review examines the potential of various antimicrobial agents, such as antimicrobial peptides, quorum-sensing inhibitors, phytoextracts, and nanoparticles, in targeting biofilms. Furthermore, we highlight the future directions for research in this area and the potential of phytotherapy for the prevention and treatment of biofilm-related infections in clinical settings.

13.
Soft comput ; : 1-13, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-37362268

RESUMO

The usage of social media is increasing by leaps and bounds in our day-to-day lives. It affects daily routines and brings a lot of change in different departments like health and education systems during the COVID-19 pandemic. Healthcare research and practice have been significantly impacted by the astounding growth of social media. Social media are changing health information management in several ways, from offering appropriate ways to enhance healthcare professional contact and share health-related knowledge and experience to facilitating the development of innovative medical research and wisdom. Social media analytics (SMAs) are efficient and effective interaction instruments that can be useful for both patients and clinicians in health interventions. Moreover, a significant portion of those involved in clinical practices (such as clinicians, professional colleges, and departments of health) are unaware of the importance of social media, its potential applications in their daily lives, as well as the possible consequences and how these will be handled. In the presented study, we proposed MCDM-based approaches known as "Criteria Importance Through Inter Correlation" (CRITIC) and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) in order to identify the effective alternative among several options and make a better decision. After extracting features from the literature review, we choose six significant and relevant features and assign weights to them using CRITIC techniques while utilizing the TOPSIS technique to rank the alternatives based on their performance values. After the implementation of both methods and evaluation procedure, it is determined that the alternative with the highest score is placed at the top and called the "best alternative," while the alternative with the lowest score is placed at the bottom and called the worst alternative. Finally, we suggest a variety of research initiatives and new research areas where the aforementioned procedures become extremely useful in evaluating SMAs and their uses in online health interventions.

14.
Heliyon ; 9(5): e15831, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37251878

RESUMO

Food neophobia, described as a reluctance to eat and or avoid new food, is a personality trait that affects food choice. Despite its potential influence on an individual's food intake, food neophobia has been poorly investigated in Bangladesh. This cross-sectional study was designed to evaluate food neophobia and its association with sociodemographic factors and food preferences in a sample of Bangladeshi university students. Five hundred students from five public universities completed the structured surveys. Food neophobia was assessed by a 10-item validated food neophobia scale with some minor modifications based on study settings. A multiple linear regression model was used to observe the factors associated with food neophobia. The mean food neophobia score among study participants was 37.45 (SD: 13.39, Range: 13-67). According to the adjusted statistical model, being female (regression coefficient, ß = 2.73), having higher monthly family income (ß = -6.64), being underweight (ß = 4.68), being overweight (ß = -4.63), having any food allergy (ß = 9.09), and a history of sickness after eating a new food item (ß = 5.16) were significantly associated with food neophobia amongst the participants. The participants' liking of various food items such as vegetables were significantly correlated with food neophobia scores. Nutrition education policies and programs are of importance to address the students' food neophobia during their tertiary education so that they maintain lifelong healthy dietary habits and consume a variety of foods to improve their physical health and well-being.

15.
Curr Med Chem ; 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37218197

RESUMO

This review focuses on recent trends in the binding study of various antimalarial agents with serum albumins in detail. Serum albumin has a significant role in the transport of drugs and endogenous ligands. The nature and magnitude of serum albumin and drug interactions have a tremendous impact on the pharmacological behavior and toxicity of that drug. Binding of drug to serum albumin not only controls its free and active concentration, but also provides a reservoir for a long duration of action. This ultimately affects drug absorption, distribution, metabolism, and excretion. Such interaction determines the actual drug efficacy as the drug action can be correlated with the amount of unbound drug. With the advancement in spectroscopic techniques and simulation studies, binding studies play an increasingly important role in biophysical and biomedical science, especially in the field of drug delivery and development. This review assesses the insight we have gained so far to improve drug delivery and discovery of antimalarials on the basis of a plethora of drug-serum protein interaction studies done so far.

16.
J Biomol Struct Dyn ; 41(23): 13724-13751, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36826451

RESUMO

We have synthesized the pyrazole-bearing Schiff base derivatives (5a-5e) and (6a-6h) then the structural confirmation was supported by various spectral analyses. The antibacterial activity of all analogs was screened against bacterial strains Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Klebsiella pneumonieae and Pseudomonas aeruginosa. In comparison to the reference drug ciprofloxacin, the lead analogs 5c and 6c showed potent activity, with MIC values of 64 µg/mL against E. coli and B. subtilis. Compound 5c showed a moderate effect with a MIC value of 128 µg/mL against B. subtilis, P. aeruginosa and K. pneumonieae, while compound 6c was against E. coli and P. aeruginosa. Furthermore, the compounds 5c and 6c displayed groove binding mode towards CT-DNA by absorption, emission, competitive fluorescence studies using EtBr, CD and time-resolved fluorescence studies. Thermodynamic parameters of analogs 5c and 6c with CT-DNA were also calculated at 298, 303 and 308K temperatures by UV-visible spectroscopy. The molecular docking studies give the docking score for all compounds with PDB codes: 1BNA and 2XCT. The MD simulation study of analogs 5c and 6c was also carried out. The pharmacokinetic and ADME properties were calculated for all of the synthesized analogs (5a-5e) and (6a-6h).Communicated by Ramaswamy H. Sarma.


Assuntos
Escherichia coli , Simulação de Dinâmica Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Bases de Schiff/química , Antibacterianos/química , Pirazóis/farmacologia , Testes de Sensibilidade Microbiana
17.
J Biomol Struct Dyn ; 41(9): 3717-3727, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35343865

RESUMO

Thromboembolic diseases are a major cause of mortality in human and the currently available anticoagulants are associated with various drawbacks, therefore the search for anticoagulants that have better safety profile is highly desirable. Compounds that are part of the dietary routine can be modified to possibly increase their anticoagulant potential. We show mannose 2,3,4,5,6-O-pentasulfate (MPS) as a synthetically modified form of mannose that has appreciable anticoagulation properties. An in silico study identified that mannose in sulfated form can bind effectively to the heparin-binding site of antithrombin (ATIII) and heparin cofactor II (HCII). Mannose was sulfated using a simple sulfation strategy-involving triethylamine-sulfur trioxide adduct. HCII and ATIII were purified from human plasma and the binding analysis using fluorometer and isothermal calorimetry showed that MPS binds at a unique site. A thrombin inhibition analysis using the chromogenic substrate showed that MPS partially enhances the activity of HCII. Further an assessment of in vitro blood coagulation assays using human plasma showed that the activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged in the presence of MPS. A molecular dynamics simulation analysis of the HCII-MPS complex showed fluctuations in a N-terminal loop and the cofactor binding site of HCII. The results indicate that MPS is a promising lead due to its effect on the in vitro coagulation rate.Communicated by Ramaswamy H. Sarma.


Assuntos
Cofator II da Heparina , Manose , Humanos , Cofator II da Heparina/química , Cofator II da Heparina/metabolismo , Manose/farmacologia , Coagulação Sanguínea , Anticoagulantes/farmacologia , Anticoagulantes/química , Heparina/farmacologia , Antitrombina III/farmacologia , Antitrombina III/fisiologia , Antitrombinas/farmacologia , Trombina/química
18.
J Biomol Struct Dyn ; 41(13): 6377-6393, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35924780

RESUMO

Hydroxychloroquine (HCQ), a quinoline based medicine is commonly used to treat malaria and autoimmune diseases such as rheumatoid arthritis. Since, human serum albumin (HSA) serves as excipient for vaccines or therapeutic protein drugs, it is important to understand the effect of HCQ on the structural stability of HSA. In this study, the binding mechanism of HCQ and their effect on stability of HSA have been studied using various spectroscopic techniques and molecular dynamic simulation. The UV-VIS results confirmed the strong binding of HCQ with HSA. The calculated thermodynamics parameters confirmed that binding is spontaneous in nature and van der Waals forces and hydrogen bonding are involved in the binding system which is also confirmed by molecular docking results. The steady-state fluorescence confirms the static quenching mechanism in the interaction system, which was further validated by time-resolved fluorescence. The synchronous fluorescence confirmed the more abrupt binding of HCQ with tryptophan residue of HSA compared to Tyr residue of HSA. Isothermal titration calorimetry (ITC) was done to validate the thermodynamics parameters of HSA-HCQ complex in one experiment, supporting the values obtained from the spectroscopic techniques. The circular dichroism (CD) demonstrated that the HCQ affected the secondary structure of HSA protein by reducing their α-helical content. The docking and molecular dynamic simulation results further helped in understanding the effect of HCQ on conformational changes of HSA. Overall, present work defined the physicochemical properties and interaction mechanism of HCQ with HSA that have extensively been elucidated by both in vitro and in silico approaches.Communicated by Ramaswamy H. Sarma.


Assuntos
Antimaláricos , Hidroxicloroquina , Humanos , Antimaláricos/farmacologia , Simulação de Acoplamento Molecular , Espectrometria de Fluorescência/métodos , Ligação Proteica , Albumina Sérica Humana/química , Dicroísmo Circular , Termodinâmica , Sítios de Ligação
19.
Healthcare (Basel) ; 10(12)2022 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-36554032

RESUMO

This study investigated the association between healthy eating behaviors and nutrition literacy in a sample of Bangladeshi adults. A cross-sectional survey was conducted among 400 adults from two districts of Bangladesh (Dhaka and Chattogram). Data were generated by in-person interviews using a structured questionnaire. The Nutrition Literacy Scale and National Dietary Guidelines for Bangladesh were used to assess nutrition literacy and healthy eating behaviors, respectively. Multiple linear regression models were used to observe the association. The mean score for healthy eating behavior was 21.8 (SD = 4.8, Range: 5−33) on a scale of 34. A moderate positive correlation was found between nutrition literacy and healthy eating behavior of participants (r = 0.28, p < 0.001). The adjusted regression model showed that a 1 unit increase in nutrition literacy reflected an increase in the healthy eating behavior score of participants by 0.22 units (ß = 0.223, p < 0.001). Findings showed an association between nutrition literacy and eating behaviors in Bangladeshi adults. Future research could be carried out to establish a causal relationship that may help inform the necessity of educational interventions for Bangladeshi adults to assist with meeting national nutrition-related targets.

20.
PLoS One ; 17(10): e0276343, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36251676

RESUMO

INTRODUCTION: The usage of dietary supplement (DS) such as vitamins, minerals, and fish oil has expanded, but there is limited data on their use by sub-populations such as university students. The study was aimed to investigate the prevalence of DS use among Bangladeshi university students and its associated factors. METHODS: A cross-sectional survey of 390 students was conducted from two public universities from Barishal Division in Bangladesh using a structured questionnaire with 72 questions divided into five sections: sociodemographic, knowledge, opinions, and attitudes, types of DS, reasons and sources for using DS, and adverse reactions after taking DS. Descriptive statistics and logistic regression were utilized to estimate the results. RESULTS: Among all the students, 15.6% students were using DS where only 7.7% of them used DS according to physicians' recommendation. Additionally, students used DS for general health and well-being, weight gaining and as a source of energy for physical and sporting activities, etc. The use of DS was significantly associated with female sex (AOR = 5.44, 95% CI: 2.18-13.52), ≥25 years age (AOR = 0.08, 95% CI: 0.01-0.67), underweight (AOR = 5.86, 95% CI: 1.95-17.62), having major illness (AOR = 6.99, 95% CI: 1.98-24.70) and good knowledge of DS (AOR = 2.64, 95% CI: 1.23-5.64). CONCLUSION: This study provides new findings on DS use and its correlates in Bangladeshi students which may be used by the policymakers to improve DS usage among students. Adaptation of an appropriate program is recommended to educate students on proper and safer ways of using DS.


Assuntos
Suplementos Nutricionais , Estudantes , Estudos Transversais , Suplementos Nutricionais/efeitos adversos , Feminino , Óleos de Peixe , Humanos , Minerais , Prevalência , Inquéritos e Questionários , Universidades , Vitaminas
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