RESUMO
Terfezia claveryi (T. claveryi) is used by traditional healers in the Middle East region to treat several diseases, including diabetes. The present study evaluated the total phenolic and investigated the blood-glucose-lowering potential of different aqueous extracts of this selected truffle using in vitro and in vivo models. The phytochemical profile was examined using UPLC-MS. The macerate and the microwave-assisted extract were the richest in phenolic compounds. All T. claveryi extracts exhibited a remarkable α-glucosidase inhibitory effect in vitro, with an IC50 of 2.43, 3.26, 5.18 and 3.31 mg/mL for the aqueous microwave-assisted extract macerate, infusion and decoction, respectively. On the other hand, in the high-fat diet alloxan-induced diabetic mice model, all tested crude aqueous extracts exhibited a significant antihyperglycemic activity (p < 0.05). Four hours after the administration of the 250 mg/kg dose, the macerate was able to induce a 29.4% blood-glucose-lowering effect compared to a 24.8% reduction induced by the infusion, which was sustained for a further two hours. The hypoglycemic effect (29.3% and 32.4%) was also recorded six hours after the administration of the single dose 500 mg/kg of the macerate and the infusion, respectively. Truffle extracts exhibited antidiabetic activity both in vitro and in vivo, providing a rationale for the traditional use as a natural hypoglycemic.
Assuntos
Diabetes Mellitus Experimental , Hipoglicemiantes , Animais , Ascomicetos , Glicemia , Cromatografia Líquida , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Camundongos , Fenóis/análise , Extratos Vegetais/química , Espectrometria de Massas em TandemRESUMO
Recently, significant advances in modern medicine and therapeutic agents have been achieved. However, the search for effective antidiabetic drugs is continuous and challenging. Over the past decades, there has been an increasing body of literature related to the effects of secondary metabolites from botanical sources on diabetes. Plants-derived metabolites including alkaloids, phenols, anthocyanins, flavonoids, stilbenoids, saponins, tannins, polysaccharides, coumarins, and terpenes can target cellular and molecular mechanisms involved in carbohydrate metabolism. In addition, they can grant protection to pancreatic beta cells from damage, repairing abnormal insulin signaling, minimizing oxidative stress and inflammation, activating AMP-activated protein kinase (AMPK), and inhibiting carbohydrate digestion and absorption. Studies have highlighted many bioactive naturally occurring plants' secondary metabolites as candidates against diabetes. This review summarizes the current knowledge compiled from the latest studies published during the past decade on the mechanism-based action of plants-derived secondary metabolites that can target various metabolic pathways in humans against diabetes. It is worth mentioning that the compiled data in this review will provide a guide for researchers in the field, to develop candidates into environment-friendly effective, yet safe antidiabetics.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Animais , Glicemia/análise , Diabetes Mellitus/sangue , Diabetes Mellitus/metabolismo , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/metabolismo , Compostos Fitoquímicos/farmacologia , Plantas/química , Plantas/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
In the quest for discovering potent antimicrobial agents with lower toxicity, we envisioned the design and synthesis of nalidixic acid-D-(+)-glucosamine conjugates. The novel compounds were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive bacteria, Gram negative bacteria and fungi. Cytotoxicity using MTT assay over L6 skeletal myoblast cell line, ATCC CRL-1458 was carried out. In vitro antimicrobial assay revealed that 1-ethyl-7-methyl-4-oxo-N-(1,3,4,6-tetra-O-acetyl-2-deoxy-D-glucopyranose-2-yl)-[1,8]-naphthyridine-3-carboxamide (5) and 1-ethyl-7-methyl-4-oxo-N-(2-deoxy-D-glucopyranose-2-yl)-[1,8]-naphthyridine-3-carboxamide(6) possess growth inhibitory activity against resistant Escherichia coli NCTC, 11954 (MIC 0.1589 mM) and Methicillin resistant Staphylococcus aureus ATCC, 33591 (MIC 0.1589 mM). Compound (5) was more active against Listeria monocytogenes ATCC 19115 (MIC 0.1113 mM) in comparison with the reference nalidixic acid (MIC 1.0765 mM). Interestingly, compound (6) had potential antifungal activity against Candida albicans ATCC 10231 (MIC <0.0099 mM). Remarkably, the tested compounds had low cytotoxic effect. This study indicated that glucosamine moiety inclusion into the chemical structure of the marketed nalidixic acid enhances antimicrobial activity and safety.
Assuntos
Anti-Infecciosos/síntese química , Desenho de Fármacos , Glucosamina/síntese química , Naftiridinas/síntese química , Anti-Infecciosos/farmacologia , Linhagem Celular , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Glucosamina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/fisiologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Mioblastos/efeitos dos fármacos , Mioblastos/fisiologia , Naftiridinas/farmacologiaRESUMO
BACKGROUND: Origanum syriacum (O. syriacum) is a very popular edible and medicinal plant in the East Mediterranean countries. The aims of the current study were to use microwave-ultrasonic assisted hydrodistillation (MUAHD) method to produce essential oils (EOs) from wild O. syriacum samples collected from four different geographical areas in The West Bank using water as a solvent, determine the phytochemical profile using GC-MS analysis and assess their antioxidant and antibacterial potential. METHODS: Essential oils were produced using MUAHD method. Gas chromatography coupled with mass spectrometer detector (GC-MS) was employed for phytochemical analysis. In vitro antibacterial and antioxidant potentials were carried out. RESULTS: Differences in the EOs yield among the four Origanum samples were observed. GC-MS analysis of EOs revealed terpenes as the major constituents; monoterpenes (22-56%) and oxygenated monoterpenes (28-57%). Thymol, α-terpinene and carvacrol represent the bulk of all phytochemicals detected by GC-MS analysis. γ-Terpinene-rich EOs, exhibited the highest antioxidant capacity. Thymol-rich EOs were found to be most effective against Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus (MRSA) (MIC 390⯵g/mL). Alpha-terpinene-rich chemotype EOs exhibited the highest inhibitory effect of Pseudomonas aeruginosa (MIC of 1560⯵g/mL). Interestingly, γ-terpinene-rich EO showed promising antibacterial properties against Enterococcus faecium (MIC 97⯵g/mL) and a powerful anti-oxidant effect (91.45% ±2.30). CONCLUSION: The current study supports the use of MUAHD as a time-saving, cost-effective, environment-friendly method for production of high quality O. syriacum EO for potential use as a natural complementary treatment and in the prevention of bacterial infections as well as oxidation by free radicals without compromising the quantity.
RESUMO
Misconception about antibiotics use among the public has been widely outlined to be a main reason for inappropriate use of antibiotics including failure to complete treatment, skipping of doses, re-use of leftover medicines and overuse of antibiotics. The study was devised to evaluate whether education might be a potential strategy to promote safer use of antibiotics and reducing self-medication. Two hundred seventy one adults were asked to complete two questionnaires; a pre and posteducation. The questionnaires comprised of three parts consisting of 17 statements assessing the knowledge on: appropriate use, safe use and resistance of antibiotics. Knowledge score was estimated by calculating the percentage of correct responses. The mean (SD) knowledge score pre-education was 59.4% (20.3). However, posteducation the score was 65.9% (17.9), p < 0.001(t-test). Knowledge scores were classified as poor, adequate and good. Posteducation, participants within poor and adequate knowledge categories were significantly shifted to the good category describing better knowledge, McNemar-χ2 = 28.7, df = 3, p < 0.001. It is concluded that using tailored education material targeting antibiotic need and use with a major aim of improving the public knowledge about antibiotics can be an effective and feasible strategy. This pilot study could be considered as the starting point for a wider scale public educational intervention study and national antibiotic campaign. However, the improvement in participant's knowledge might not reflect an actual change in antibiotics-seeking behaviour or future retention of knowledge. Future research should seek to assess the impact of education on participant's behaviour.
RESUMO
Sulphonylurea compounds have versatile activities such as antidiabetic, diuretic, herbicide, oncolytic, antimalarial, antifungal and anticancer. The present study describes the design, synthesis and in vivo testing of novel glycosylated aryl sulfonylurea compounds as antihyperglycaemic agents in streptozocine-induced diabetic mice. The rational for the introduction of the glucosamine moiety is to enhance selective drug uptake by pancreatic ß-cells in order to decrease the cardiotoxic side effect commonly associated with sulfonylurea agents. 2-Deoxy-2-(4-chlorophenylsulfonylurea)-D-glucopyranose was found to be the most potent antihyperglycaemic agents among the synthesized compounds in diabetic mice. This investigation indicates the importance of this novel class as potential antihyperglycaemic agents.
Assuntos
Técnicas de Química Sintética , Desenho de Fármacos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Compostos de Sulfonilureia/química , Compostos de Sulfonilureia/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Avaliação Pré-Clínica de Medicamentos , Glicosilação , Hipoglicemiantes/síntese química , Masculino , Camundongos , Estrutura Molecular , Compostos de Sulfonilureia/síntese químicaRESUMO
Normally, skeletal muscle accounts for 70-80% of insulin-stimulated glucose uptake in the postprandial hyperglycemia state. Consequently, abnormalities in glucose uptake by skeletal muscle or insulin resistance (IR) are deemed as initial metabolic defects in the pathogenesis of type 2 diabetes mellitus (T2DM). Globally, T2DM is growing in exponential proportion. The majority of T2DM patients are treated with sulfonylureas in combination with other drugs to improve insulin sensitivity. Glycosylated sulfonylureas (sulfonylurea-glucosamine analogues) are modified analogues of sulfonylurea that have been previously reported to possess antidiabetic activity. The aim of this study was to evaluate the impact of glycosylated sulfonylureas on the insulin signalling pathway at the molecular level using L6 skeletal muscle cell (in vitro) and extracted soleus muscle (ex vivo) models. To create an in vitro model, insulin resistance was established utilizing a high insulin-glucose approach in differentiated L6 muscle cells from Rattus norvegicus. Additionally, for the ex vivo model, extracted soleus muscles, adult Sprague-Dawley rats were subjected to a solution containing 25 mmol L-1 glucose and 100 mmol L-1 insulin for 24 hours to induce insulin resistance. After insulin resistance, compounds under investigation and standard medicines (metformin and glimepiride) were tested. The differential expression of PI3K, IRS-1, PKC, AKT2, and GLUT4 genes involved in the insulin signaling pathway was evaluated using qPCR. The evaluated glycosylated sulfonylurea analogues exhibited a significant increase in the gene expression of insulin-dependent pathways both in vitro and ex vivo, confirming the rejuvenation of the impaired insulin signaling pathway genes. Altogether, glycosylated sulfonylurea analogues described in this study represent potential therapeutic anti-diabetic drugs.
RESUMO
COVID-19 has spread and developed into a pandemic disease, forcing countries to impose challenging protocols and lockdowns. This study assessed shopping, food consumption behavior, and feelings in Jordan and several Arab countries during the COVID-19 pandemic. A cross-sectional web-based survey among the Middle East population was conducted using an online questionnaire between July and September 2022. Participants were requested to answer a standardized and validated structured questionnaire. Demographic information, shopping behavior information, and mental health data were requested. A total of 542 respondents were included in the study. During COVID-19 quarantine, participants (68.6%) reported decreased shopping frequency and buying more food than usual (37.5%). Cereals and legumes were the primary food types stored by participants (76.9%). Multiple logistic regression revealed the age of the participant as a significant factor affecting storing of food (being ≤ 25 years old (OR = 0.456, p value = 0.038)). 75.7% of female participants eat less frequently in restaurants than usual. In contrast, among males, 48.5% reported that they eat at restaurants less frequently than usual. The country of residency and gender were the significant factors affecting negative feelings and emotions. Participants in countries other than Jordan had a higher negative feeling score (Beta = 0.086, p value = 0.042). Furthermore, females had a higher negative feeling score (Beta = -0.128, p value = 0.003) as the negative feelings score for females was 3.58 (SD = 5.443). On the other hand, it was 2.10 (SD = 5.091) for males. The COVID-19 pandemic has altered Jordanians' attitudes, shopping, and food consumption habits. Although positive behaviors have improved, such as shopping less frequently, eating home-cooked meals, and dining with family, frequent snacking and food storage have increased. Finally, public awareness of shopping and food consumption habits should be promoted.
Assuntos
COVID-19 , Comportamento Alimentar , Estilo de Vida , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Masculino , Feminino , Estudos Transversais , Adulto , Comportamento Alimentar/psicologia , Pessoa de Meia-Idade , Jordânia/epidemiologia , Pandemias , Inquéritos e Questionários , Adulto Jovem , SARS-CoV-2 , AdolescenteRESUMO
BACKGROUND: Although there is little information available to quantify the use of complementary and alternative medicine (CAM), growing evidence suggests that CAM prevalence among patients seeking infertility treatment is increasing worldwide. There are many products available on the market and many infertile patients demand information about CAM from their health care providers. This paper investigates the prevalence of CAM use among infertile couples in Jordan. Additionally, trends and factors contributing to CAM use for infertility treatment among these couples have been evaluated. METHODS: A face-to-face questionnaire inquiring demographic information, use of CAM for medical conditions, in general, and types of CAM used for infertility treatment, in specific, was completed by one thousand twenty one infertile patients attending at two types of facilities; in vitro Fertilization (IVF) centers at both public and private hospitals and infertility private clinics. Both types of facilities were distributed in different areas of Amman, the capital city of Jordan. The study was conducted between May and August 2012. RESULTS: Our results show that CAM therapies for infertility treatment were encountered in 44.7% of the study sample. The vast majority of CAM users were females. The most commonly used CAM therapies were herbs and spiritual healing. A clear correlation between the use of CAM for infertility versus the use of CAM for other chronic medical conditions has been found. CONCLUSIONS: The prevalence of CAM use for infertility treatment in Jordan is relatively high, particularly among young females, well educated and with a low income, in consistence with the studies reported elsewhere. Herbs and spiritual healing are widely used among patients in adjunct to conventional medical interventions. As CAM use is prevalent among patients, there is a clear need for health providers to become more aware of this phenomenon and for further research in this field.
Assuntos
Terapias Complementares/estatística & dados numéricos , Infertilidade/terapia , Fitoterapia/estatística & dados numéricos , Extratos Vegetais/uso terapêutico , Terapias Espirituais/estatística & dados numéricos , Adolescente , Adulto , Instituições de Assistência Ambulatorial , Características da Família , Feminino , Fertilização in vitro , Hospitais , Humanos , Jordânia , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Espiritualidade , Inquéritos e Questionários , Adulto JovemRESUMO
Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics (cefixime, levofloxacin and gentamicin) with Lysobacter enzymogenes (L. enzymogenes) bioactive proteases present in the cell- free supernatant (CFS) have been investigated against the Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative Escherichia coli (E. coli O157:H7). Results indicated that L. enzymogenes CFS had maximum proteolytic activity after 11 days of incubation and higher growth inhibitory properties against MSSA and MRSA compared to E. coli (O157:H7). The combination of L. enzymogenes CFS with cefixime, gentamicin and levofloxacin at sub-MIC levels, has potentiated their bacterial inhibition capacity. Interestingly, combining cefixime with L. enzymogenes CFS restored its antibacterial activity against MRSA. The MTT assay revealed that L. enzymogenes CFS has no significant reduction in human normal skin fibroblast (CCD-1064SK) cell viability. In conclusion, L. enzymogenes bioactive proteases are natural potentiators for antimicrobials with different bacterial targets including cefixime, gentamicin and levofloxacin representing the beginning of a modern and efficient era in the battle against multidrug-resistant pathogens.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Humanos , Levofloxacino/farmacologia , Peptídeo Hidrolases , Cefixima , Escherichia coli , Virulência , Antibacterianos/farmacologia , Meticilina , Staphylococcus aureus , Gentamicinas/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Jordan is rich in the flora of ethnobotanical importance. This scoping review aims to highlight the ethnopharmacological value of Jordanian medicinal plants using the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of one hundred twenty-four articles published between 2000 and 2022 obtained from PubMed, EBSCO, and Google Scholar databases were included in this review. These plants own several classes of secondary bioactive metabolites, including alkaloids, flavonoids, phenolics, and terpenes. Jordanian plants exhibited potential therapeutic activity against various tumors, bacterial infections, elevated blood glucose levels, hyperlipidemia, platelets aggregation disorders, and gastrointestinal disorders. Phytochemicals' biological activities depend on their structures, parts used, methods of extraction, and evaluation model. In conclusion, this review highlights the need of researching Jordan's abundant naturally occurring medicinal plants and their phytochemicals as novel lead molecules in drug discovery and development. Studying active phytochemicals for disease treatment will help develop drugs for safe treatment and cure in the future.
RESUMO
Factors associated with antibiotic use, resistance and safety have been well recognized worldwide in the literature. Nevertheless, only few studies have been conducted in Jordan in this area. The aim of this study was to assess knowledge, behavior and attitude toward antibiotics use among adult Jordanians. The study represents a cross sectional survey using an interviewer administered questionnaire. Data collected from a random sample of 1141 adult Jordanians, recruited at different settings, regarding their knowledge about the effectiveness of, resistance toward, and self medications with antibiotics against bacterial, viral and parasitic diseases. 67.1% believed that antibiotics treat common cold and cough. 28.1% misused antibiotics as analgesics. 11.9% of females showed inadequate knowledge about the safe use of antibiotics during pregnancy and nursing. 28.5% kept antibiotics at home for emergency use and 55.6% use them as prophylaxis against infections. 49.0% use left-over antibiotics without physicians' consultation while 51.8% use antibiotics based on a relative advice. 22.9% of physicians prescribe antibiotics over the phone and >50.0% routinely prescribe antibiotics to treat common cold symptoms. Our findings indicated that young adults showed unsatisfactory knowledge of proper antibiotic use. Therefore, there is an urge for educational programs using all media means.
RESUMO
COVID-19 infection is a global pandemic health emergency. This contagious disease was caused by the Severe Acute Respiratory Syndrome Coronavirus2 (SARSCoV-2) which is mutating over time. In 2021, the Delta variant became the most dominant transmissible form. During the crisis, human practice and knowledge were critical in the overall efforts to encompass the outbreak. A cross-sectional, web-based approach was conducted among adults in Jordan to quantify knowledge, attitude, and practices towards SARS-CoV-2 (Delta variant). This research was carried out between 15th April and 15th of May 2021. The study questionnaire consisted of four sections including the participant's demographics, knowledge, practices and attitude. Comparative evaluation of responses was accomplished using a scoring system. Respondents who scored above the mean score (60%) on the item measured were categorized as knowledgeable, having a positive attitude, and good practices. Participants were allocated to one of the three groups; medical, non-medical and others (unemployed and housewives). Data collected was analyzed using Statistical Package for Social Sciences (SPSS) version 23.0 software. A variance test to assess the statistical difference between groups was used. Pearson's chi-squared test was applied to compare the variables and identify significant predictors. Of the participants, 308 (66%) were in the age group of 18-25yrs, 392 (84.1%) females, 120 (25.8%) employed and 346 (74.2%) unemployed. The principle source of knowledge was social media (291, 62.4%). Interestingly, participants had adequate overall knowledge. The mean knowledge score was 22.6 (± 0.19), 20.6 (± 0.19), and 21.3 (± 0.18) for the medical, the non-medical and the others group, respectively. Also, participants showed a positive attitude and good practices towards SARS-CoV-2 (Delta variant). The mean practice score for medical, the non-medical and the others groups was 7.35 (± 0.25), 7.38 (± 0.24), 7.35 (± 0.24) and the mean attitude score was 10.8 (± 0.16), 9.4 (± 0.21), 9.5 (± 0.22), respectively. The studied groups generally had good knowledge, positive attitudes and good practices about SARS-CoV-2 (Delta variant). This was expected due to the authorities' successful management of the pandemic and the high educational level of the Jordanian society, bearing in mind the economic and social impact of COVID-19 disease.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Adolescente , Adulto Jovem , Adulto , SARS-CoV-2/genética , COVID-19/epidemiologia , Estudos Transversais , Jordânia/epidemiologiaRESUMO
An electroanalytical electrode for the detection of albendazole (ABZ) active ingredient in pharmaceutical dosage form and in contaminated animal-derived products was developed using a glassy carbon electrode modified with platinum-palladium nanoparticles. The electro-catalytic performance of the bimetallic-modified glassy carbon electrode was compared with its bare counterpart. Under optimized conditions, the modified electrode revealed two well-resolved anodic peak currents at 1.10 and 1.23 V using differential pulse voltammetry. Pure ABZ, as well as ABZ in spiked foods (milk and chicken), were detected with little interference from the food matrix. This electrode demonstrated high sensitivity and applicability, with a lower limit of detection of 0.08 µmol L-1 in aqueous solution and 10 µmol L-1 in the contaminated ground chicken and 100 µmol L-1 in the contaminated milk sample. The fabricated sensor is low in cost and appropriate for the estimation of albendazole in tablet dosage forms and biological samples, and so can act as a quality control tool in the pharmaceutical and food industry.
Assuntos
Nanopartículas Metálicas , Nanocompostos , Animais , Platina , Carbono , Paládio , Albendazol , Eletrodos , Preparações FarmacêuticasRESUMO
BACKGROUND: The relationship between obesity and various chronic diseases is well documented. In Jordan, the prevalence of overweight (30.0%) and obesity (38.8%) among females is on the rise, encouraging many adults to rely on alternative health care methods to manage their weight. AIMS: We explored the status of complementary and alternative medicine use for weight management among adult females in Jordan and the possible relationship between complementary and alternative medicine use and body mass index. METHODS: An interviewer-administered, structured questionnaire was used to collect data on the use and safety of complementary and alternative medicine for weight management from 858 women in 2015. Responses were coded and analysed using SPSS, version 20. RESULTS: Around 40% of the respondents reported using some form of complementary and alternative medicine for weight management. Commercial dietary supplements (31.2%), herbal remedies (26.7%) and folk remedies (18.0%) were commonly used. Green tea and fibre tablets were the most widely used herbal supplements. Logistic regression analysis indicated that overweight participants are more frequent complementary and alternative medicine users compared to obese. Relatives and friends were the main sources of information about complementary and alternative medicine. Only 31.9% of women believed that complementary and alternative medicine modalities were safe; around half believed they were not safe during pregnancy (52.5%) and lactation (48.0%). Only 49.7% were aware of side-effects and 41.5% of drug interactions. CONCLUSION: This study revealed that complementary and alternative medicine is often used for weight management. Awareness of the safe use of complementary and alternative medicine with other medications and during pregnancy and lactation should be addressed.
Assuntos
Manutenção do Peso Corporal , Terapias Complementares/psicologia , Terapias Complementares/estatística & dados numéricos , Adolescente , Adulto , Índice de Massa Corporal , Terapias Complementares/efeitos adversos , Feminino , Humanos , Jordânia , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto JovemRESUMO
Herein we report the design, synthesis and biological evaluation of structurally modified ciprofloxacin, norfloxacin and moxifloxacin standard drugs, featuring amide functional groups at C-3 of the fluoroquinolone scaffold. In vitro antimicrobial testing against various Gram-positive bacteria, Gram-negative bacteria and fungi revealed potential antibacterial and antifungal activity. Hybrid compounds 9 (MIC 0.2668 ± 0.0001 mM), 10 (MIC 0.1358 ± 00025 mM) and 13 (MIC 0.0898 ± 0.0014 mM) had potential antimicrobial activity against a fluoroquinolone-resistant Escherichia coli clinical isolate, compared to ciprofloxacin (MIC 0.5098 ± 0.0024 mM) and norfloxacin (MIC 0.2937 ± 0.0021 mM) standard drugs. Interestingly, compound 10 also exerted potential antifungal activity against Candida albicans (MIC 0.0056 ± 0.0014 mM) and Penicillium chrysogenum (MIC 0.0453 ± 0.0156 mM). Novel derivatives and standard fluoroquinolone drugs exhibited near-identical cytotoxicity levels against L6 muscle cell-line, when measured using the MTT assay.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Desenho de Fármacos , Fluoroquinolonas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fluoroquinolonas/síntese química , Fluoroquinolonas/química , Glicosilação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Penicillium chrysogenum/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
This work describes the engineering of a feasible, sensitive, and specific colorimetric assay for the detection of Staphylococcus aureus (S. aureus) extracellular protease production, using a tailored agar-based readout platform. Firstly, S. aureus protease production was evaluated using different culture media. Maximum proteolytic activity was achieved after 24â¯h of incubation in brain heart infusion (BHI) broth at 37⯰C, as confirmed using azo-casein and Sigma's non-specific protease activity assays. Secondly, to enhance proteolysis detection, novel agar-based platform readouts for S. aureus proteases were developed. Clear proteolytic zones were observed after 48â¯h of incubation at 37⯰C, using an agar-agar platform supplemented with 3% skim milk as a non-specific protease substrate. Thirdly, the colorimetric visualization of S. aureus proteolytic zones was evaluated using three different techniques, namely, the use of chromogenic media, dye flooding over the platform, and protease staining prior to testing. Colorimetric sensing of proteolysis was achieved by applying a Bromocresol Purple-colored protease solution on a skim milk plate count agar-PEG 4000 readout platform. Color change (yellow to burgundy) indicated a positive readout after 15â¯min of incubation. The lowest limit of S. aureus detection was 102 CFU mL-1. Moreover, direct detection of S. aureus BHI culture was achieved by sensing the pH change because of protease production, using bromothymol blue dye. A light-green color represented a positive readout. A direct relationship between S. aureus culture concentration and color change was observed, with a detection limit as low as 103 CFU mL-1. Examination of blind samples of Escherichia coli and S. aureus showed the potential of this assay to specifically detect S. aureus in situ. Therefore, the developed approach is anticipated to help detect S. aureus for biomedical applications.
Assuntos
Colorimetria/métodos , Peptídeo Hidrolases/análise , Staphylococcus aureus/enzimologia , Staphylococcus aureus/isolamento & purificação , Concentração de Íons de Hidrogênio , Peptídeo Hidrolases/metabolismo , Proteólise , Staphylococcus aureus/citologiaRESUMO
BACKGROUND: Breast cancer is the second leading cause of cancer-related deaths among women in the Western World. METHOD: Upon diagnosis and treatment in the preinvasive state, the five years survival rate levitate up to 93%, making early detection crucial for dedicative diagnosis and treatment. Currently, mammography is the most efficacious diagnostic modality. However, this technique does not match the ultimate sensitivity. Other routinely used biomarkers include tumor size, histological type, nuclear and cellular characteristics, mitotic index, vascular invasion, hormonal and axillary lymph node status were not good enough to predict the course of cancer. To date, researchers revealed a change in the level of some proteinases in breast cancer tissue and reported the role of these proteinases in tumor aggressiveness and patient response to therapy. CONCLUSION: This review summarizes the potential role of serine proteinases (including urokinasedependent plasminogen activator and kallikreins) and zinc metalloproteinases (including matrix metalloproteinase and A disintegrin and metalloproteinase) as either a prognostic and/or diagnostic breast cancer biomarkers. These proteinases plus genetic biomarkers could be implemented in the development of multiplex bio sensing platform toward early breast cancer detection, diagnosis, monitor progression and therapeutic success.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Peptídeo Hidrolases/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Feminino , Humanos , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismoRESUMO
Aristolochia maurorum L. of Jordanian origin has been investigated phytochemically, quantitatively, and biologically. Three atypical alkaloids, namely aristolochic acid I (1), aristolochic acid II (2) and aristolochic acid IIIa (3), have been isolated and identified. Of these known 1-phenanthrenecarboxylic acids, 2 and 3 are reported for the first time from this species. The identified compounds 1-3 were first evaluated biologically as cytotoxic agents against the brine shrimp lethality test (BST), in which compound 1 was found to be the most potent (LC50, 4.9 microg/mL). The antiplatelet activity of the methanolic extracts, the acidic fractions of aerial and root parts, and the identified compounds 1-3 were evaluated using an automatic platelet aggregometer and coagulation tracer (APACT 2). Using external reference standards, and a reverse-phase isocratic method, the distribution of aristolochic acid I and aristolochic acid II in different plant parts of Aristolochia maurorum L. during flowering stage was analyzed by PDA-HPLC. A quantitative comparison between two previously reported extraction methods was also made. Roots were found to be the main storage of aristolochic acid I and aristolochic acid II during flowering stage with about 0.22 and 0.108% (w/w), respectively.
Assuntos
Capsicum/virologia , Herbicidas/farmacologia , Vírus de Plantas/efeitos dos fármacos , Plantas/metabolismo , Plantas/virologia , Capsicum/efeitos dos fármacos , Carbono/metabolismo , Clorofila/análise , Fotossíntese/efeitos dos fármacosRESUMO
UNLABELLED: Neuronal Nitric Oxide synthase (nNOS) is an attractive challenging target for the treatment of various neurodegenerative disorders. To date, several structure-based studies were conducted to search novel selective nNOS inhibitors. OBJECTIVE: Discovery of novel nNOS lead scaffolds through the integration of ligand-based threedimensional (3D) pharmacophore (s) with quantitative structure-activity relationship model. METHOD: The pharmacophoric space of ten structurally diverse sets acquired from 145 previously reported nNOS inhibitors was scrutinize to fabricate representative pharmacophores. Afterwards, genetic algorithm together with multiple linear regression analysis was applied to find out an optimal pharmacophoric models and 2D physicochemical descriptors able to produce optimal predictive QSAR equation (r(2) 116 =0.76, F = 353, r(2) LOO = 0.69, r(2) PRESS against 29 external test ligands =0.51). A minimum of three binding modes between ligands and nNOS binding pocket rationalized by the emergence of three pharmacophoric models in the QSAR equation were illustrated. The QSAR-selected pharmacophores were validated by receiver operating characteristic curves analysis and afterward invested as a tool for screening national cancer institute (NCI) database. RESULTS: Low micro molar novel nNOS inhibitors were revealed. CONCLUSION: Two structurally diverse compounds 148 and 153 demonstrated new scaffolds toward the discovery of potent nNOS inhibitors.