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The greatest environmental issue of the twenty-first century is climate change. Human-caused greenhouse gas emissions are increasing the frequency of extreme weather. Carbon dioxide (CO2) accounts for 80% of human greenhouse gas emissions. However, CO2 emissions and global temperature have risen steadily from pre-industrial times. Emissions data are crucial for most carbon emission policymaking and goal-setting. Sustainable and carbon-neutral sources must be used to create green energy and fossil-based alternatives to reduce our reliance on fossil fuels. Near-real-time monitoring of carbon emissions is a critical national concern and cutting-edge science. This review article provides an overview of the many carbon accounting systems that are now in use and are based on an annual time frame. The primary emphasis of the study is on the recently created carbon emission and eliminating sources and technology, as well as the current application trends for carbon neutrality. We also propose a framework for the most advanced naturally available carbon neutral accounting sources capable of being implemented on a large scale. Forming relevant data and procedures will help the "carbon neutrality" plan decision-making process. The formation of pertinent data and methodologies will give robust database support to the decision-making process for the "carbon neutrality" plan for the globe. In conclusion, this article offers some opinions, opportunities, challenges and future perspectives related to carbon neutrality and carbon emission monitoring and eliminating resources and technologies.
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Dióxido de Carbono , Gases de Efeito Estufa , Humanos , Dióxido de Carbono/análise , Efeito Estufa , Biodiversidade , Temperatura , Tecnologia , Recursos NaturaisRESUMO
Low cost and an easy technique for the synthesis of palladium nanoparticles (PdNPs) was developed. Glucosamine was used to stabilize palladium precursor (PdCl2) into palladium nanoparticles. Several analytical techniques were used for the determination of morphology, crystalline structure; size, capping, and composition of synthesize palladium nanoparticles. The UV-visible spectroscopy SPR peak (Surface Plasmon Resonance) at 284â¯nm revealed synthesis of PdNPs. Energy dispersive X-ray (EDX) and X-ray diffraction (XRD) studies proved the elemental composition and crystalline structure of the synthesized palladium nanoparticles respectively. The average particle sizes (5.5â¯nm) were obtained by using the 1â¯M glucosamine solution, with a fixed amount of PdCl2 (4â¯mM). Moreover, the as synthesized PdNPs was evaluated against Gram negative bacterial E. which shows tremendous antibacterial activity as compare to tobramycin standard antibiotics. It's mechanistically found that PdNPs damage cell membrane and caused imbalance of metabolism system of the cell as a result production of reactive oxygen species (ROS). Thus, these finding revealed that cells become leaky and all organelles come out from cells, finally caused death of the E. coli. Addition, the as prepared PdNPs also showed excellent catalytic activities toward reduction of methylene blue and 4-nitrophenol.Thus, glucosamine mediated PdNPs having dual functions biomedical as well as intoxicating catalyst for industries.
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Antibacterianos/metabolismo , Glucosamina/metabolismo , Nanopartículas Metálicas/ultraestrutura , Paládio/metabolismo , Substâncias Redutoras/metabolismo , Membrana Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Excipientes/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Nanopartículas Metálicas/química , Espécies Reativas de Oxigênio/metabolismo , Espectrometria por Raios X , Análise Espectral , Ressonância de Plasmônio de Superfície , Difração de Raios XRESUMO
The aim of the present study was to examine the effect of gamma radiation on levofloxacin. Powder form of levofloxacin was subjected to different radiation doses (25, 50, 75, 100 and 125kGy) of Cobalt-60 source in a Gammacell-220 at a rate of 8.5 Gray/hr. The effect of radiation has been investigated with the aid of different spectroscopic techniques (UV-Vis, FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and by antibacterial activities. UV data did not reveal significant changes in the structure of levofloxacin which is supported by scanning electron microscopy. However, X-rays diffraction shows a change in crystallinity of levofloxacin to an amorphous structure and this has been reflected on the morphology of this compound as indicated by SEM images. The antibacterial activities, on the other hand, reveal resistance of irradiated levofloxacin against bacteria, where some bacteria were highly affected by the irradiated drug. Similarly, FT-IR data show some changes in the functional groups principal absorption bands, in the IR spectrum, at frequencies 3286, 2846, 1716 and 1620 cm-1 for the O-H stretching band of quinolone, C-H stretching band, and C=O stretching band of carboxylic and pyridine. In addition, new peaks appeared which were not seen in the non-irradiated spectrum. In conclusion, some changes occurred in levofloxacin drug with the passage of radiation but the drug was chemically stable.
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Antibacterianos/efeitos da radiação , Raios gama , Levofloxacino/efeitos da radiação , Esterilização/métodos , Antibacterianos/química , Bactérias Gram-Negativas/efeitos da radiação , Bactérias Gram-Positivas/efeitos da radiação , Levofloxacino/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pós , Estereoisomerismo , Propriedades de SuperfícieRESUMO
A dimeric naphthoquinone namely dihydrodyspyrole R (1) was purified once more from Diospyros lotus. Dihydrodyspyrole R and chloroform fractions were evaluated for their effects on the reversion of multidrug resistance (MDR). The compounds (1) and extract exhibited promising MDR reversing effect in a dose-dependent manner against mouse T-lymphoma cell line. Molecular docking of compound 1 revealed the correlation between in-silico with in-vitro results. The molecular docking results showed that compound 1 is bind closely where co-crystal ligand of P-gp is present. But usually, computational investigation predicts that, if a compound gives lesser score then compound will exhibit good activity. Hence, the docking scores of compound 1 are the near to the Rhodamine. It is conclude that there are certain important structural features of compound 1which are responsible for the inhibiting potency of P-gp from mice. The computational Petra/Osiris/Molinspiration (POM) analysis confirms the possibility of use of compound 1 without side effect or less toxicity risks.
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Diospyros , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lotus , Naftoquinonas/química , Extratos Vegetais/química , Animais , Linhagem Celular Tumoral , Cristalografia por Raios X/métodos , Resistência a Múltiplos Medicamentos/fisiologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Camundongos , Simulação de Acoplamento Molecular/métodos , Naftoquinonas/isolamento & purificação , Naftoquinonas/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Raízes de PlantasRESUMO
The formation of metal nanoparticles is one of the most vast and intensifying research areas in favor of prospective applications for the advancement of new technologies. It is a well-founded, significant feature of green chemistry that making marvelous interconnection between nano-biotechnology and microbial biotechnology. In the present research, the aqueous extract of medicinally important plant Coptis Chinensis (in Chinese called "gold thread") was applied for the synthesis of gold nanoparticles (Au-NPs). The crystalline structure, size, shape and dispersion of Au-NPs were confirmed by using various characterization techniques i.e. X-ray Diffraction (XRD), High Resolution Transmission Electron Microscope (HRTEM) and Energy Dispersive X-ray (EDX). Well dispersed face centered cubic crystalline structures were obtained in the this contribution. The possible phyto-chemicals involved in the reduction and stabilization of Au-NPs were confirmed by Fourier Transform Infrared Spectroscopy (FT-IR). The prepared NPs were tested against highly drug resistance bacterium Escherichia coli both in light and dark. The results illustrated that the antibacterial efficiency of photo irradiated Au-NPs was several times higher than in dark Au-NPs. The zone of inhibition for irradiated Au-NPs was19 ± 0.5 mm, which was higher than in dark 14 ± 0.4 mm. This high antibacterial activity of photo irradiated Au-NPs are due to the production of reactive oxygen species which is responsible for the inhibition of bacteria.
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Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Ouro/efeitos da radiação , Luz , Nanopartículas Metálicas/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/química , Coptis/química , Farmacorresistência Bacteriana , Ouro/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
BACKGROUND: The BK Polyomavirus (BKPyV) and JC polyomavirus (JCPyV) infections are widespread in human population and have been associated with severe kidney and brain disorders, respectively. The viruses remain latent primarily in reno-urinary tract, reactivating only in case of a compromised immune system. The seroepidemiology and molecular prevalence of BKPyV and JCPyV have been widely studied both in healthy and immunocompromised patients worldwide. However, data regarding the prevalence of these viruses in the immunocompetent or apparently healthy Pakistani population is lacking. Herein, we present the first ever report on quantitative prevalence of BKPyV and JCPyV in the peripheral blood of a randomly selected cohort of healthy Pakistani population. METHODS: A total of 266 whole blood samples were examined. The subjects were divided into three age groups: ≤ 25 years (young), 26-50 years (middle) and ≥ 51 years (elder). Absolute real time PCR assay was designed to quantify the BKPyV and JCPyV viral copy numbers in the range of 106 to 100 copies/mL. RESULTS: Overall, BKPyV was detected in 27.1% (72/266) individuals while JCPyV in 11.6% (31/266) indicating significant difference (p < 0.005) in the distribution of these two viruses. The prevalence of BKPyV significantly decreased from 51% (49/96) in young age group to 8.2% (7/85) in eldest age group. Whereas, JCPyV positivity rate slightly increased from 8.3% (8/96) in young age group to 11.8% (10/85) in elder age group. The median viral load was calculated as 6.2 log and 3.38 log copies/mL of blood for BKPyV and JCPyV, respectively. Notably, no significant difference in viral load of either of the subtypes was found between different age groups. CONCLUSION: The current study provides an important baseline data on the prevalence and viral load of circulating BKPyV and JCPyV in Pakistani population. The prevalence and viral load of BKPyV was comparatively higher than JCPyV. The prevalence of BKPyV significantly decreased with increase in age while JCPyV positivity rate slightly increased with increasing age. Viral load of both BKPyV and JCPyV was not correlated with the individual ages.
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Vírus BK/isolamento & purificação , Voluntários Saudáveis , Vírus JC/isolamento & purificação , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sangue/virologia , Portador Sadio/epidemiologia , Portador Sadio/virologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , Adulto JovemRESUMO
Plant phenolics are known to display many pharmacological activities. In the current study, eight phenolic compounds, e.g., luteolin 5-O-ß-glucoside (1), methyl rosmarinate (2), apigenin (3), vicenin 2 (4), lithospermic acid (5), soyasaponin II (6), rubiadin 3-O-ß-primeveroside (7), and 4-(ß-d-glucopyranosyloxy)benzyl 3,4-dihydroxybenzoate (8), isolated from various plant species were tested at 0.2 mm against carbonic anhydrase-II (CA-II) and urease using microtiter assays. Urease inhibition rate for compounds 1 - 8 ranged between 5.0 - 41.7%, while only compounds 1, 2, and 4 showed a considerable inhibition over 50% against CA-II with the IC50 values of 73.5 ± 1.05, 39.5 ± 1.14, and 104.5 ± 2.50 µm, respectively, where IC50 of the reference (acetazolamide) was 21.0 ± 0.12 µm. In silico experiments were also performed through two docking softwares (Autodock Vina and i-GEMDOCK) in order to find out interactions between the compounds and CA-II. Actually, compounds 6 (30.0%) and 7 (42.0%) possessed a better binding capability toward the active site of CA-II. According to our results obtained in this study, among the phenolic compounds screened, particularly 1, 2, and 4 appear to be the promising inhibitors of CA-II and may be further investigated as possible leads for diuretic, anti-glaucoma, and antiepileptic agents.
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Inibidores da Anidrase Carbônica/farmacologia , Fenóis/farmacologia , Urease/antagonistas & inibidores , Domínio Catalítico , Simulação por Computador , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
The dramatic increase in healthcare costs has become a significant burden to this era. Many patients are unable to access medication because of the high price of drugs. Genetic engineering has made advances to increase the yield, titer, and productivity in the bio-based production of chemicals, materials of interest, and identification of innovative targets for drug discovery. Currently, the production of homoglutamate (α-Aminoadipic acid) involves petrochemical routes that are costly with low yield and often not suitable for industrial production. Here, we established the development of NADH-dependent homoglutamate by engineering NADH-dependent phenylalanine dehydrogenase (PDH) from Thermoactinomyces intermedius, which provides a novel tool for in-vivo metabolic engineering and in-vitro catalysis. Based on computational insight into the structure, we proposed the site-specific directed mutagenesis of the two important residues of PDH through docking simulations by AutoDock Vina which elucidated the binding mode of PDH with α-Ketoadipic acid and ligands. Our results demonstrated that the catalytic efficiency Km/Kcat of the final mutant Ala135Arg showed a 3-fold increase amination activity towards the ketoadipic acid as compared to the other mutant Gly114Arg, a double mutant Gly114Arg/Ala135Arg, and wild type TiPDH. Furthermore, we have introduced formate dehydrogenase as a cofactor regenerative system in this study which further made this study economically viable. Our study unfolds the possibility of biosynthesis of other non-proteinogenic amino acids that might be valuable pharmaceutical intermediaries.
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Aminoácido Oxirredutases , Ácido Glutâmico , NAD , Thermoactinomyces , Aminoácido Oxirredutases/genética , Ácido Glutâmico/biossíntese , NAD/metabolismo , Engenharia de Proteínas , Thermoactinomyces/enzimologiaRESUMO
Introduction: The genus Euphorbia is known to contain diterpenoids, and several isolated compounds which exhibited biological activities including significant multidrug resistance reversal effects. This work is focused on the isolation, in vitro and in silico studies of two natural bio-active flavonoids (1 & 2) isolated from Euphorbia pulcherrima bark for the very first time.Methods: The phytochemical investigation resulted in the identification of two flavonoids: 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl)-6-methoxy-4H-chromen-4-one (1) and 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-6-methoxy-4H-chromen-4-one (2), which were isolated for the first time from Euphorbia pulcherrima.Results: The chemical structures of the two isolated compounds were confirmed by 1H NMR, 13C NMR, and ESI-HRMS spectral data. The Bioactivity activity of these compounds was evaluated; results revealed that compounds 1 & 2 exhibit promising urease inhibitory potential with IC50 values of 15.3 ± 2.13 µM and 19.0 ± 2.43 µM, respectively, whereas the positive control thiourea had an IC50 of 21.0 ± 0.23 µM. Similarly, these compounds were also evaluated against the tyrosinase enzyme; results showed that compound 1 displays significant inhibitory activity with an IC50 value of 48.7 ± 2.19 µM, whereas compound 2 exhibited a moderate effect with an IC50 value of 74.8 ± 1.79 µM, when compared with the standard (alpha-kojic acid, IC50 = 47.6 ± 0.67 µM). Additionally, compounds 1 and 2 also exhibited anti-glycation and phosphodiesterase inhibitory activities.Conclusion: Studies dealing with the drug like properties such as in silico screening (docking study) was also carried out to discover the structural features of both compounds 1 and 2. Results indicated that the docking scores of compounds 1 and 2 are in agreement with their IC50 values. Key messagesIsolation and characterization of two bioactive flavonoids (1 and 2) from Euphorbia pulcherrima.In silico and in vitro enzyme inhibition studies were conducted to identify the therapeutic potential of flavonoids 1 and 2.Drug-like properties were calculated to discover important pharmacophoric features.
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Euphorbia , Euphorbia/química , Flavonoides/farmacologia , Humanos , Extratos Vegetais/farmacologiaRESUMO
To prospect an isozyme-specific, effective inhibitor against the physiologically-crucial enzyme phosphodiesterase 1 (PDE1), phytochemicals from Pistacia integerrima galls were screened. The chloroform fraction of gall extract was subjected to column chromatographic which led to the isolation of compound 1, elucidated to be 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one (a flavone). In vitro and in silico PDE1 inhibitory activity of the compound 1 was investigated. EDTA, a known PDE1 inhibitor, was used as the reference. The flavone exhibited in vitro attenuation towards snake venom PDE1. IC50 response was superior to the standard chelator. An in silico molecular docking study was carried out using 3D structure of PDE1 to study the binding interactions of compound 1. The docking study predicted that flavone had a lower binding affinity (-7.6 kcal/mol) and total energy (-95 kcal/mol) score compared to EDTA. The minimal energy associated with the ligand-protein complex implied that isolated compound 1 can serve as a therapeutic agent against PDE1 enzyme-provoked ailments like asthma, hypertension, schizophrenia, and erectile dysfunction.
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Pistacia , Ácido Edético , Flavonas , Simulação de Acoplamento Molecular , Diester Fosfórico Hidrolases , Pistacia/químicaRESUMO
BACKGROUND: Cancer being a genetically heterogeneous and complex disease and the available therapies are not very effective, rendering them the predominant cause of mortality across the world. The discovery of new anticancer drugs with higher efficacy and milder side effects is a great challenge for health professionals. OBJECTIVE: The current study focused on the anticancer potential of two known dimeric napthoquiones, diospyrin (1) and 8-hydroxydiospyrin (2) isolated from the roots of Diospyros lotus. METHODS: In vitro Epstein-Barr-Virus (EVA) an early antigen activation assay was used to evaluate the antitumor potential of tested compounds followed by a two-stage carcinogenesis assay on mouse skin for anti-carcinogenic effect. Compounds were also assessed for their multidrug resistance reversal potential. The in vitro heatinduced protein denaturation assay was used for the anti-inflammatory effect of the tested compounds. RESULTS: Both compounds evoked marked cytotoxic activity with IC50 of 47.40 and 36.91 ppm, respectively. In Epstein-Barr-Virus (EVA) early antigen activation assay compounds 1 and 2 showed IC50 values of 426 ppm and 412 ppm, respectively. The tested compounds showed 60% survival rate of the lymphoblastoid Raji cells at a concentration of 1000 (mol / ratio 32 pmol TPA). In a two-stage carcinogenesis assay on mouse skin, both compounds significantly delayed the formation of papillomas on mouse skin. Compound 1 showed 50% effect at 14th week, whereas compound 2 exerted the same effect at 13th week, while both provoked 100% effect at 20th week. Both compounds significantly attenuated thermal-induced protein denaturation with EC50 values of 298 and 264 µg/mL, respectively. The dimeric napthoquiones were evaluated for their effects on the reversion of Multidrug-Resistant (MDR) cell lines mediated by P-glycoprotein using rhodamine 123 dye-based exclusion screening test on human mdr1 gene transfected thymic lymphoma L5178 cell line. The compounds 1 and 2 exhibited promising MDR reversal effect in a dose-dependent manner against mouse T-lymphoma cell line. Docking results also showed that both compounds have good docking statistics as compared with standard. CONCLUSION: Both the compounds demonstrated marked anti-tumor, anti-carcinogenic, and MDR reversal effects with significant attenuation of thermal-induced denaturation of the protein. These compounds may explain the traditional uses of D. lotus which might be effective anticancer agents.
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Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Diospyros/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Naftoquinonas/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antígenos Virais/imunologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Artemia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Masculino , Camundongos , Simulação de Dinâmica Molecular , Estrutura Molecular , Naftoquinonas/química , Naftoquinonas/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/químicaRESUMO
In the presence of Fe3O4 nano-fibers, we prepared SiO2-Zn@Fe2O3 hybrid Nano-fibers through a novel and simple one-pot redox reaction between ZnSO4 & SiO2. The Fe3O4 exterior nano-fibers would be homogenously covered by SiO2 coating to arrange a distinctive core-shell construction and then Zn nanoparticles are intercalated in the covering of SiO2. The synthesized nanofibers were tested for photodegradation of methylene blue (MB). The result showed that 99 % MB was degraded in 60 min. Furthermore, the antibacterial potential of SiO2-Zn@Fe2O3 nanofibers was tested against E. coli and S. aureus bacteria both in light and dark. The impact of different analysis such as Reactive oxygen species (ROS) analysis, irradiation effect on bacterial inhibition, concentration effect of SiO2-Zn@Fe2O3 nanofibers and reduction of DPPH studied. The findings clearly demonstrate that ROS is produced in the presence of SiO2-Zn@Fe2O3 nanofibers in bacterial cells and is responsible for their inhibition. Findings have shown that synthesized nanostructures can also increase the stability of DPPH radicals with increasing concentrations of nanomaterials, making them a strong candidate for DPPH reduction. The overall results show that the efficacy of SiO2-Zn@Fe2O3 nanofibers for inhibition was more pronounced than that of individual iron oxides.
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Nanofibras , Fotoquimioterapia , Escherichia coli , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Dióxido de Silício , Staphylococcus aureus , ZincoRESUMO
BACKGROUND AND AIM: Foot-and-mouth disease (FMD) has been occurring in Algeria since 2014, when an outbreak was announced in Setif, a district in the eastern region of the country. The problem was apparently resolved with the help of vaccination. However, in 2015, 2016, and 2018, FMD recurred. The veterinary authorities and media educated breeders on how to recognize the clinical signs and how to report the disease. This study aimed to evaluate the knowledge and recognition of FMD by farmers and breeders. Moreover, an assessment of the behavior of cattle and sheep owners and herders following FMD cases is examined. MATERIALS AND METHODS: A cross-sectional survey was conducted from June to October 2018 to evaluate the perception of cattle and sheep owners and breeders regarding FMD in the Northern regions of Algeria, using questionnaires. RESULTS: One hundred questionnaires were distributed; 71 were collected. Data showed that all the responders claimed to know about the disease, while more than half of the owners/herders claimed that they knew the clinical symptoms of FMD and mentioned fever, hypersalivation, lameness, and vesicles. Fewer than half (42%) (30/71) took some measures to prevent the disease, while more than half (58%) (41/71) did not take any measures in 2018. No one claimed to have reported the disease to authorities in 2018, while more than half had done so in 2014. CONCLUSION: It appears that experienced farmers recognized the clinical signs of FMD, while an academic background was not conclusively necessary for the identification of the clinical signs of the disease. Concerning the assessment of risk-associated behavior in the event of FMD occurrence, the responses of the breeders were not significantly different from those of risk-associated behaviors in the event of an epidemic. Farmers and breeders expressed similarity in terms of communicating the appearance of the disease in their livestock; the majority of them seemed to be aware of the importance of reporting the disease to local authorities, especially in 2014, when the disease first occurred. This behavior is encouraged by refund and technical assistance policies by the veterinary authorities, but in 2018, no disease was reported due to fear of slaughtering and economic loss.
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INTRODUCTION: Natural products derived from medicinal plants provide beneficial cancer chemotherapeutic drugs. Bioactive constituents from plants are explored for their anticancer properties. METHODS: Three known compounds (deacetylbaccatin III, tasumatrol B, and taxawallin J) were isolated from Taxus wallichiana. Compounds were screened against four cancer cell lines, such as eA498, HepG2, NCI-H226, and MDR 2780AD. Cytotoxic activity was evaluated using MTT assay against cancer cell lines. RESULTS: Tasumatrol B showed good cytotoxic activity conducted for the improvement of inhibiting potential of these compounds against the cancer drug target protein (EGFR tyrosine kinase enzyme). The docking study showed that all compounds have binding affinities and interaction profile with the receptor tyrosine kinase. DISCUSSION: The study suggests that these compounds could be used for the discovery of novel inhibitors against the target receptors for the treatment of cancer.
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Adipic acid (AA) is an important dicarboxylic acid used for the manufacture of nylon and polyurethane plastics. In this study, a novel adipic acid biosynthetic pathway was designed by extending the cis,cis-muconic acid (MA) biosynthesis through biohydrogenation. Enoate reductase from Clostridium acetobutylicum (CaER), an oxygen-sensitive reductase, was demonstrated to have in vivo enzyme activity of converting cis,cis-muconic acid to adipic acid under microaerobic condition. Engineered Escherichia coli strains were constructed to express the whole pathway and accumulated 5.8⯱â¯0.9â¯mg/L adipic acid from simple carbon sources. Considering the different oxygen demands between cis,cis-muconic acid biosynthesis and its degradation, a co-culture system was constructed. To improve production, T7 promoter instead of lac promoter was used for higher level expression of the key enzyme CaER and the titer of adipic acid increased to 18.3⯱â¯0.6â¯mg/L. To decrease the oxygen supply to downstream strains expressing CaER, Vitreoscilla hemoglobin (VHb) was introduced to upstream strains for its ability on oxygen obtaining. This attempt further improved the production of this novel pathway and 27.6⯱â¯1.3â¯mg/L adipic acid was accumulated under microaerobic condition.
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Adipatos/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Oxigênio/farmacologia , Ácido Sórbico/análogos & derivados , Aerobiose , Proteínas de Bactérias/farmacologia , Biocatálise , Vias Biossintéticas , Carbono/farmacologia , Clostridium acetobutylicum/enzimologia , Técnicas de Cocultura , Hidrogenação , Ácido Salicílico/metabolismo , Ácido Sórbico/metabolismo , Hemoglobinas Truncadas/farmacologiaRESUMO
Urease enzyme is responsible for gastric cancer, peptic ulcer, hepatic coma, and urinary stones in millions of people across the world. So, there is a strong need to develop new and safe antiurease drugs, particularly from natural sources. In search for new and effective drugs from natural sources bioassay-guided fractionation and isolation of Berberis glaucocarpa Stapf roots bark resulted in the isolation and characterization, on the basis of 1D and 2D NMR data, of two bisbenzylisoquinoline alkaloids, oxyacanthine (1) and tetrandrine (2), followed by urease inhibition studies. Crude extract, all the subfractions and the isolated compounds 1 and 2 displayed excellent urease enzyme inhibition properties in vitro. The antiurease nature and possible mode of action for compounds 1 and 2 were verified and explained through their molecular docking studies against jack-bean urease enzyme. Half-maximum inhibitory concentration (IC50) was calculated for compounds 1 and 2. The IC50 value was found to be 6.35 and 5.51 µg/mL for compounds 1 and 2, respectively. Both compounds 1 and 2 have minimal cytotoxicity against THP-1 monocytic cells.
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Graphene-based materials have attracted a significant attention in constructing hybrid systems for drug delivery with enhanced antimicrobial activities. In our work, we demonstrated the formation of silver nanoparticles (AgNPs) on graphene oxide (GO) using tobramycin (TOB), an aminoglycoside antibiotic, as reducing and decorating agent. The TOB decorated GO AgNPs (TOB-GO-Ag) composite was used as an antibacterial agent against multi-drug resistant Gram-negative E-coli (BL21 DE3). The reversal of surface potential from -30â¯mV (GO) to +20â¯mV confirms the successful reduction of GO by TOB. Atomic force microscopy (AFM) and high-resolution transmission electron microscopic (HRTEM) analyses confirmed the formation of uniformly distributed AgNPs on the reduced GO with an approximate particle size of 5â¯nm. The as-synthesized nanocomposite displayed significant antibacterial activity as compared to pure AgNPs and TOB. The positively charged TOB-GO-Ag interacts with the negatively charged E. coli membrane and inhibit bacterial growth by the antibacterial actions of the released silver, GO and tobramycin from the TOB-GO-Ag composite. The significant loss of bacterial membrane potential from -52⯱â¯2â¯mV (control) to -2⯱â¯1â¯mV (treated) indicates a severe cell wall damage caused by TOB-GO-Ag composite. Furthermore, fluorescence study also demonstrated a severe membrane disruption in bacterial cells treated with TOB-GO-Ag composite as compared to pure AgNPs and GO. In conclusion, the development of such hybrid systems would help in enhancing the efficacy of available drugs and eradicating the emerging bacterial resistance.
Assuntos
Antibacterianos/química , Grafite/química , Nanopartículas Metálicas/química , Nanocompostos/química , Prata/química , Tobramicina/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Parede Celular/química , Parede Celular/efeitos dos fármacos , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Células HEK293 , Humanos , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Nanocompostos/toxicidade , Óxidos/química , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Tobramicina/farmacologiaRESUMO
Utilizing novel approaches for the green synthesis of metal nanoparticles are of great importance. Therefore, we reported biogenic synthesis of silver nanoparticles (AgNPs) using extracts of Leptolyngbya strain JSC-1, and their significant applications against pathogenic bacteria and cancerous HeLa cell line. The biofabricated AgNPs were characterized by UV-visible spectroscopy, FTIR, SEM, TEM, DLS and zeta-potential. The as prepared AgNPs were assessed for inhibition of bacterial growth and induction of apoptosis in HeLa cells by different doses of AgNPs was evaluated. UV-visible spectroscopy and FTIR of AgNPs demonstrated the surface plasmon resonance at 413 nm and interaction among extract and nanoparticles, respectively. Electron microscopy revealed the morphology and DLS demonstrated size distribution of the particles (10-100 nm). Zeta potential values were between -47 and 0 mV, indicating stability of the particles. Proliferation of HeLa cells was significantly inhibited and severe cytotoxicity with higher intracellular uptake were observed after applying high concentration of AgNPs. Efficient inhibition zones (17 ± 2 and 21 ± 2 mm) were produced at maximum concentration (100 µl from 1 mg ml-1 stock of AgNPs) for Staphylococcus aureus and Escherichia coli, respectively. These findings reveal that the biofabricated AgNPs possess strong antibacterial activity and ability to induce apoptosis in cancer cell line (HeLa).
Assuntos
Antibacterianos , Apoptose/efeitos dos fármacos , Misturas Complexas/química , Cianobactérias/química , Escherichia coli/crescimento & desenvolvimento , Nanopartículas Metálicas/química , Prata , Staphylococcus aureus/crescimento & desenvolvimento , Antibacterianos/química , Antibacterianos/farmacologia , Células HeLa , Humanos , Prata/química , Prata/farmacologiaRESUMO
The study of molecular interactions of drug-protein are extremely important from the biological aspect in all living organisms, and therefore such type of investigation hold a tremendous significance in rational drug design and discovery. In the present study, the molecular interactions between paromomycin (PAR) and human serum albumin (HSA) have been studied by different biophysical techniques and validated by in-silico approaches. The results obtained from Ultraviolet-visible spectroscopy (UV) and Fourier transform infrared spectroscopy (FT-IR) demonstrated a remarkable change upon the complexation of PAR with HSA. Circular Dichroism (CD), Dynamic Light Scattering (DLS) and Resonance Rayleigh scattering (RRS) results revealed a significant secondary structure alteration and reduction of hydrodynamic radii upon the conjugation of PAR with HSA. The fluorescence spectroscopy results also apparently revealed the static quenching mechanism. The number of binding sites, binding constants, and Gibbs free energy values were calculated to illustrate the nature of intermolecular interactions. Similarly, the in-silico docking and molecular dynamics simulation clearly explain the theoretical basis of the binding mechanism of PAR with HSA. The experimental and docking approaches suggested that PAR binds to the hydrophobic cavity site I of HSA. The finding of present investigation will provide binding insight of PAR and associated alterations in the stability and conformation of HSA.
Assuntos
Paromomicina/química , Albumina Sérica Humana/química , Dicroísmo Circular , Estabilidade de Medicamentos , Difusão Dinâmica da Luz , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , TermodinâmicaRESUMO
BACKGROUND: Polyphenols are organic compounds widely found in plants and possess many diverse biological activities. In the current study, eleven polyphenolic compounds [rutin (1), trans-ferulic acid (2), epigallaocatechin gallate (3), fumaric acid (4), chlorogenic acid (5), gallic acid (6), trans-resveratrol (7), propyl gallate (8), (+)-catechin (9), quercetin (10), and kaempferol-3-O-ß-D-galactoside (11)] have been evaluated for their in vitro inhibitory activity against phosphodiesterase- 1 (PDE-1). The active compounds 1, 5, 6, and 7 possessed IC50 values of 173.90 ± 2.58, 36.67 ± 1.60, 325.19 ± 3.62, and 323.81 ± 4.25 µM, respectively. In silico experiments were performed to elucidate the binding patterns of inhibitor molecules with the active sites of the enzymes. RESULT: Molecular docking studies have shown that compounds 1 and 5 have better docking results than standard inhibitor (EDTA) against the PDE-1. In conclusion, chlorogenic acid, rutin, gallic acid, and resveratrol could be promising PDE-1 inhibitors and leads to identify new drug candidates against PDE-1-associated disorders.