Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1501
M. Barakat, M. Al-Najjar, S. Abdulrazzaq, Wamidh H. Talib, Tamara Athamneh
Background: Probiotics are a mixture of good live bacteria and/or yeasts that naturally survive in our bodies. Recently, loads of studies have focused on their role in the immune system and digestive tract. Accordingly, there are many commercially available probiotic products in the market. This study examines the immunostimulatory effect of commercially available-probiotic conditioned medium (PCM) on RAW264.7 murine macrophages. Methods: Probiotic conditioned medium has been prepared by culturing the commercially available probiotic in a cell culture medium overnight at 37°C, followed by centrifugation and filter-sterilization to be tested on RAW264.7 murine macrophages. The immunostimulatory effect of different ratios (50, 75, 100) of PCM was examined using MTT assay, pro-inflammatory cytokine (tumor necrosis factor TNF-alpha) production in macrophages., migration, and Phagocytosis assays. Results: At all the examined PCM ratios, the percentages of cell viability were >80%. Regarding the migration scratch, TNF-alpha and phagocytosis assays, PCM demonstrated a concentration-dependent pattern in the immunostimulatory effect. However, the ratio of 100 PCM illustrated a significant (p-value<0.05) stimulatory effect compared to the positive and negative control. Conclusion: The findings of this study confirm the stimulatory activity of probiotic conditioned medium, which may contribute directly to the immune-boosting effect of the probiotic supplements.
{"title":"The Immunostimulatory Effect of Probiotic Conditioned Medium on RAW264.7 Murine Macrophages","authors":"M. Barakat, M. Al-Najjar, S. Abdulrazzaq, Wamidh H. Talib, Tamara Athamneh","doi":"10.35516/jjps.v16i2.1501","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1501","url":null,"abstract":"Background: Probiotics are a mixture of good live bacteria and/or yeasts that naturally survive in our bodies. Recently, loads of studies have focused on their role in the immune system and digestive tract. Accordingly, there are many commercially available probiotic products in the market. This study examines the immunostimulatory effect of commercially available-probiotic conditioned medium (PCM) on RAW264.7 murine macrophages. \u0000Methods: Probiotic conditioned medium has been prepared by culturing the commercially available probiotic in a cell culture medium overnight at 37°C, followed by centrifugation and filter-sterilization to be tested on RAW264.7 murine macrophages. The immunostimulatory effect of different ratios (50, 75, 100) of PCM was examined using MTT assay, pro-inflammatory cytokine (tumor necrosis factor TNF-alpha) production in macrophages., migration, and Phagocytosis assays. \u0000Results: At all the examined PCM ratios, the percentages of cell viability were >80%. Regarding the migration scratch, TNF-alpha and phagocytosis assays, PCM demonstrated a concentration-dependent pattern in the immunostimulatory effect. However, the ratio of 100 PCM illustrated a significant (p-value<0.05) stimulatory effect compared to the positive and negative control. \u0000Conclusion: The findings of this study confirm the stimulatory activity of probiotic conditioned medium, which may contribute directly to the immune-boosting effect of the probiotic supplements.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46727369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1467
Y. Al-Hiari, Shereen Arabiyat, V. Kasabri, I. Hamdan, I. Almasri, M. Yasin, Dalya Al-Saad
Background: Cancer is one of the greatest troubling maladies currently. It is believed that it is the second reason for death following cardiovascular maladies. Owing to the multiplicity of its types, stages and genetic basis, there is no existing drug to cure all types of cancer. Resistance to present drugs and severe adverse effects are other challenges in the struggle against cancer. In such pursuit, fluoroquinolones (FQs) have the potential as antiproliferative compounds due to safety, low cost, and absence of resistance. Aims: In this study, we aim to synthesize biologically active compounds that have dual anticancer and anti-lipase potential. Sixteen compounds were prepared, fully characterized, and studied through identification of IC50 values against the highly susceptible cancer cell lines. Methods: In this work we are concerned with synthesizing biologically active compounds that belong to fluoroquinolones (FQs) with dual anti-colorectal cancer and anti-lipase activity, owing to association between cancer and obesity, conduct titration and docking experiments to validate our hypothesis. Results: In vitro findings indicated that these compounds demonstrated promising anticancer activity against tested cell lines in micromolar range with a potency comparable to cisplatin. Compound 11 exhibited approximately doubled potency compared to cisplatin against SW620 colorectal cancer cell line with IC50 3.2 μM which proposes FQs as potent antiproliferative agents. The synthesized Fluoroquinolone (FQ) compounds were further screened for their in vitro anti-lipase potential. The findings demonstrated that all the screened compounds have demonstrated remarkable anti-lipase activity, as compared to control molecule orlistat. Compound 9 exhibited comparable activity to orlistat against pancreatic lipase with IC50 0.4 μM which proposes FQs as potent pancreatic lipase inhibitors. Conclusions: The anticancer potential of these derivatives is referred to their ability to inhibit Topo II which indicates that chelation is the mechanism of inhibition of Topo II emphasized with titration and docking experiments.
{"title":"Metal Chelators as Anticancer Approach: Part I; Novel 7-Anisidine Derivatives with Multidentate at 7-8 Carbons of Fluoroquinolone Scaffold as Potential Chelator Anticancer and Antilipolytic Candidates","authors":"Y. Al-Hiari, Shereen Arabiyat, V. Kasabri, I. Hamdan, I. Almasri, M. Yasin, Dalya Al-Saad","doi":"10.35516/jjps.v16i2.1467","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1467","url":null,"abstract":"Background: Cancer is one of the greatest troubling maladies currently. It is believed that it is the second reason for death following cardiovascular maladies. Owing to the multiplicity of its types, stages and genetic basis, there is no existing drug to cure all types of cancer. Resistance to present drugs and severe adverse effects are other challenges in the struggle against cancer. In such pursuit, fluoroquinolones (FQs) have the potential as antiproliferative compounds due to safety, low cost, and absence of resistance. \u0000Aims: In this study, we aim to synthesize biologically active compounds that have dual anticancer and anti-lipase potential. Sixteen compounds were prepared, fully characterized, and studied through identification of IC50 values against the highly susceptible cancer cell lines. \u0000Methods: In this work we are concerned with synthesizing biologically active compounds that belong to fluoroquinolones (FQs) with dual anti-colorectal cancer and anti-lipase activity, owing to association between cancer and obesity, conduct titration and docking experiments to validate our hypothesis. \u0000Results: In vitro findings indicated that these compounds demonstrated promising anticancer activity against tested cell lines in micromolar range with a potency comparable to cisplatin. Compound 11 exhibited approximately doubled potency compared to cisplatin against SW620 colorectal cancer cell line with IC50 3.2 μM which proposes FQs as potent antiproliferative agents. The synthesized Fluoroquinolone (FQ) compounds were further screened for their in vitro anti-lipase potential. The findings demonstrated that all the screened compounds have demonstrated remarkable anti-lipase activity, as compared to control molecule orlistat. Compound 9 exhibited comparable activity to orlistat against pancreatic lipase with IC50 0.4 μM which proposes FQs as potent pancreatic lipase inhibitors. \u0000Conclusions: The anticancer potential of these derivatives is referred to their ability to inhibit Topo II which indicates that chelation is the mechanism of inhibition of Topo II emphasized with titration and docking experiments.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43306100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1497
Fedaa Adaileh
Introduction: Most of the cytotoxic anticancer drugs belong to substances with both low solubility in aqueous fluids and poor cellular uptake, which lead to lack of specific therapy with apparent side effects. Therefore, there is a need to develop a novel drug delivery that can remotely and selectively release their payload. Curcumin(CUR) is an antibiotic, also a powerful inhibitor of the proliferation of several tumor cells. Aims: The aim of the present work is to highlight and discussed hyaluronic acid (HA ) to be grafted with Mono-6-deoxyl-6-ethylenediamino-γ-cyclodextrin (ɣ-CD-EDA) to shape a hydrogel that ought to structure inclusion complexes with curcumin, bettering its water-solubility and serving as a model drug delivery system Methods: Distinct copolymers had been organized HA grafted with ɣ-cyclodextrin (ɣ-CD-EDA) to form a hydrogel with various HA: ɣ-CD-EDA ratios and characterized, by means of 1H-NMR spectroscopy, zeta potential, Thermogravimetry analysis) TGA) Differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). Furthermore, drug loading Encapsulation efficiency (EE%), and release kinetics, and stability. Also, cytotoxicity and uptake were assessed by flow cytometry, MTT assay and confocal laser microscopy. Wound healing activity was once improved using three cell MDA-MB-231, MCF-7, and fibroblast. Measuring the effect of HA-γ-CD-EDA1-CUR, γ-CD-EDA1-CUR, and CUR free on the Production and Secretion of inflammatory cytokines Result: CUR loading potential used to be at once correlated with extended HA-ɣ-CD-EDA composition and morphological adjustments have been discovered upon CUR binding. The host substances and their CUR inclusion complexes are no longer cytotoxic, and consequently beneficial for CUR and drug delivery. Moreover, HA-γ-CD-EDA1-CUR, γ-CD-EDA1-CUR, and CUR wound healing activity was once improved, and human promonocytic THP-1 cells produce inflammatory mediators such as IL-1β, IL10,IL8, TNF-α,IRAKI and IL6 results showed that the combination HA-γ-CD-EDA1-CUR could be suitable to reduce inflammation and the complex promoted the anti-inflammatory effect by the inhibition of inflammatory mediators. Conclusion: HA grafted with ɣ-cyclodextrin (ɣ-CD-EDA) to form a hydrogel was designed, formulated, and full characterized. Nanoparticles were stable at physiological pH and have released payload. Encapsulation of CUR into polymer increased its selectivity, distribution, and accumulation into the cancer cells. HA-CD-EDA1conjugated curcumin if incorporated in suitable matrix has a potential utility for treatment of wound, and down regulation in THP-1 cells.
{"title":"Crosslinking of Water-Soluble Cyclodextrin with Hyaluronic Acid for Targeted Drug Delivery","authors":"Fedaa Adaileh","doi":"10.35516/jjps.v16i2.1497","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1497","url":null,"abstract":"Introduction: Most of the cytotoxic anticancer drugs belong to substances with both low solubility in aqueous fluids and poor cellular uptake, which lead to lack of specific therapy with apparent side effects. Therefore, there is a need to develop a novel drug delivery that can remotely and selectively release their payload. Curcumin(CUR) is an antibiotic, also a powerful inhibitor of the proliferation of several tumor cells. \u0000Aims: The aim of the present work is to highlight and discussed hyaluronic acid (HA ) to be grafted with Mono-6-deoxyl-6-ethylenediamino-γ-cyclodextrin (ɣ-CD-EDA) to shape a hydrogel that ought to structure inclusion complexes with curcumin, bettering its water-solubility and serving as a model drug delivery system \u0000Methods: Distinct copolymers had been organized HA grafted with ɣ-cyclodextrin (ɣ-CD-EDA) to form a hydrogel with various HA: ɣ-CD-EDA ratios and characterized, \u0000by means of 1H-NMR spectroscopy, zeta potential, Thermogravimetry analysis) TGA) Differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). Furthermore, drug loading Encapsulation efficiency (EE%), and release kinetics, and stability. Also, cytotoxicity and uptake were assessed by flow cytometry, MTT assay and confocal laser microscopy. Wound healing activity was once improved using three cell MDA-MB-231, MCF-7, and fibroblast. Measuring the effect of HA-γ-CD-EDA1-CUR, γ-CD-EDA1-CUR, and CUR free on the Production and Secretion of inflammatory cytokines \u0000Result: CUR loading potential used to be at once correlated with extended HA-ɣ-CD-EDA composition and morphological adjustments have been discovered upon CUR binding. The host substances and their CUR inclusion complexes are no longer cytotoxic, and consequently beneficial for CUR and drug delivery. Moreover, HA-γ-CD-EDA1-CUR, γ-CD-EDA1-CUR, and CUR wound healing activity was once improved, and human promonocytic THP-1 cells produce inflammatory mediators such as IL-1β, IL10,IL8, TNF-α,IRAKI and IL6 results showed that the combination HA-γ-CD-EDA1-CUR could be suitable to reduce inflammation and the complex promoted the anti-inflammatory effect by the inhibition of inflammatory mediators. \u0000Conclusion: HA grafted with ɣ-cyclodextrin (ɣ-CD-EDA) to form a hydrogel was designed, formulated, and full characterized. Nanoparticles were stable at physiological pH and have released payload. Encapsulation of CUR into polymer increased its selectivity, distribution, and accumulation into the cancer cells. HA-CD-EDA1conjugated curcumin if incorporated in suitable matrix has a potential utility for treatment of wound, and down regulation in THP-1 cells.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42533292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1489
D. Sabbah
Background: The phosphatidylinositol 3-kinase (PI3Kα) has been spotlighted as a potential oncogene and therapeutic target for anticancer drug design. Objective: Target compounds were designed employing ligand- and structure-based drug design approaches to address the effect of the compounds’ backbones and functionalities on their biological activity. Methods: Synthesis of the targeted compounds, biological evaluation tests against human cancer cell lines, and molecular docking studies. Results: Fortunately, 20 novel series of diverse scaffolds were prepared and characterized by means of FT-IR, 1H and 13C NMR, HRMS, and elemental analysis. In addition, the identity of one core nucleus was successfully interpreted with the aid of X-ray crystallography. Biological activity of prepared compounds was investigated in vitro against human cancer cell lines. Results that these compounds inhibit cell proliferation and induce apoptosis through an increase in caspase-3 activity and a decrease in DNA cellular content. Furthermore, ligand-based pharmacophore modeling showed that the newly synthesized analogues match PI3Kα inhibitors fingerprint and the molecular docking studies against PI3Kα revealed that the analogues fit PI3Kα kinase catalytic domain and form H-bonding with key binding residues. Conclusion: The harvested series exhibited a potential PI3Kα inhibitory activity in human cancer cell lines.
{"title":"Progress in the Design and Development of Phosphoinositide-3-Kinase (PI3Kα) Inhibitors","authors":"D. Sabbah","doi":"10.35516/jjps.v16i2.1489","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1489","url":null,"abstract":"Background: The phosphatidylinositol 3-kinase (PI3Kα) has been spotlighted as a potential oncogene and therapeutic target for anticancer drug design. \u0000Objective: Target compounds were designed employing ligand- and structure-based drug design approaches to address the effect of the compounds’ backbones and functionalities on their biological activity. \u0000Methods: Synthesis of the targeted compounds, biological evaluation tests against human cancer cell lines, and molecular docking studies. \u0000Results: Fortunately, 20 novel series of diverse scaffolds were prepared and characterized by means of FT-IR, 1H and 13C NMR, HRMS, and elemental analysis. In addition, the identity of one core nucleus was successfully interpreted with the aid of X-ray crystallography. Biological activity of prepared compounds was investigated in vitro against human cancer cell lines. Results that these compounds inhibit cell proliferation and induce apoptosis through an increase in caspase-3 activity and a decrease in DNA cellular content. Furthermore, ligand-based pharmacophore modeling showed that the newly synthesized analogues match PI3Kα inhibitors fingerprint and the molecular docking studies against PI3Kα revealed that the analogues fit PI3Kα kinase catalytic domain and form H-bonding with key binding residues. \u0000Conclusion: The harvested series exhibited a potential PI3Kα inhibitory activity in human cancer cell lines.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47541583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1510
B. Rahhal, Isra N. Taha, Insaf Najajreh, W. Basha, Hamzeh Alzabadeh, A. Zyoud, Areen Sharaga, Zanab Alratrout, Nima Yunis, Ola Kanaan, Jenan Raddad, Tasneem Yousef
Purpose: Man used various natural materials as a remedy for the treatment of various diseases and recently witnessed a vastly growing and renewed interest in herbal medicine globally. In Palestinian folk medicine, Crataegus aronia, Rosmarinus officinalis known as rosemary and Nigella sativa is used as a diuretic and for treatment of hypertension. This study aimed to assess the preliminary phytochemical properties and the diuretic effect of the aqueous extracts of these plants in mice after its intraperitonial administration. Methods: It is an experimental trial applied on mice (n=8, Male, CD-1, weight range: [25-30 gram]), which are divided into two groups (4 in each). The first group administered with the plant extract (500 mg/kg), and the second with normal saline as negative control group. Then urine output and electrolyte contents were quantified up to 6 hours for the three groups and then compared to the control one. Results: Preliminary phytochemical screening reveals the presence of tannins, alkaloids and flavoniods as major phytoconstituents in aqueous extract. Significant diuresis was noted in those received the aqueous extract of Crataegus aronia (p < 0.05) compared to controls. Moreover, aqueous extract had an acidic pH and a mild increase in the electrolyte excretion (Na, K).On the contrary, the aqueous extracts from the Rosemary and Nigella sativa showed no diuretic activity. Conclusions: Our results revealed that Crataegus aronia aqueous extract has a significant potential diuretic effect. Further studies are needed to evaluate this diuretic effect in the relief of diseases characterized by volume overload.
{"title":"Phytochemical Screening and Diuretic Activity of selected Palestinian Medicinal plants in Mice using an Aqueous Extract Division of Physiology, Pharmacology and Toxicology","authors":"B. Rahhal, Isra N. Taha, Insaf Najajreh, W. Basha, Hamzeh Alzabadeh, A. Zyoud, Areen Sharaga, Zanab Alratrout, Nima Yunis, Ola Kanaan, Jenan Raddad, Tasneem Yousef","doi":"10.35516/jjps.v16i2.1510","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1510","url":null,"abstract":"Purpose: Man used various natural materials as a remedy for the treatment of various diseases and recently witnessed a vastly growing and renewed interest in herbal medicine globally. In Palestinian folk medicine, Crataegus aronia, Rosmarinus officinalis known as rosemary and Nigella sativa is used as a diuretic and for treatment of hypertension. This study aimed to assess the preliminary phytochemical properties and the diuretic effect of the aqueous extracts of these plants in mice after its intraperitonial administration. \u0000Methods: It is an experimental trial applied on mice (n=8, Male, CD-1, weight range: [25-30 gram]), which are divided into two groups (4 in each). The first group administered with the plant extract (500 mg/kg), and the second with normal saline as negative control group. Then urine output and electrolyte contents were quantified up to 6 hours for the three groups and then compared to the control one. \u0000Results: Preliminary phytochemical screening reveals the presence of tannins, alkaloids and flavoniods as major phytoconstituents in aqueous extract. Significant diuresis was noted in those received the aqueous extract of Crataegus aronia (p < 0.05) compared to controls. Moreover, aqueous extract had an acidic pH and a mild increase in the electrolyte excretion (Na, K).On the contrary, the aqueous extracts from the Rosemary and Nigella sativa showed no diuretic activity. \u0000Conclusions: Our results revealed that Crataegus aronia aqueous extract has a significant potential diuretic effect. Further studies are needed to evaluate this diuretic effect in the relief of diseases characterized by volume overload.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41809653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1498
F. Williams
Our research is utilizing the zebrafish model to study molecular processes and animal models of human diseases. These studies discussed here start to assess how different bath salts and methamphetaminecause death upon overdose by addressing the molecules that may bind to the illicit drugs. We have accomplished this by developing an in vivo photo-affinity labelling (PAL) system and studying the drugs in our system. The zebrafish has been lauded as a unique and powerful tool to examine development in a vertebrate animal and address molecular aspects of human disease for decades. We will examine recent published data from our laboratory utilizing the PAL system we developed.
{"title":"The Use of Zebrafish and in Vivo PAL as a Novel Discovery Platform for Psychoactive Agents","authors":"F. Williams","doi":"10.35516/jjps.v16i2.1498","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1498","url":null,"abstract":"Our research is utilizing the zebrafish model to study molecular processes and animal models of human diseases. These studies discussed here start to assess how different bath salts and methamphetaminecause death upon overdose by addressing the molecules that may bind to the illicit drugs. We have accomplished this by developing an in vivo photo-affinity labelling (PAL) system and studying the drugs in our system. The zebrafish has been lauded as a unique and powerful tool to examine development in a vertebrate animal and address molecular aspects of human disease for decades. We will examine recent published data from our laboratory utilizing the PAL system we developed.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42673999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1508
Alaa Abuawad
Infectious diseases represent major health and economic challenges globally. Emergence of multiple drug-resistant bacteria in the community and hospital has become a worldwide concern that requires novel approaches for rapid diagnosis and treatment. Metabolomics approach is a powerful tool providing important chemical information about the cellular phenotype of living systems, and the changes in their metabolic pathways in response to various perturbations. Metabolomics has become an important tool to study host-pathogen interactions and to discover potential novel therapeutic targets. In this study, untargeted LC-MS metabolic profiling was applied to differentiate between the impact of the secretome of the Gram-positive S. aureus SH1000 and Gram-negative P. aeruginosa PAO1 bacterial pathogens on THP-1 macrophages. The results showed that S. aureus and P. aeruginosa secretome affected alanine, aspartate and glutamate metabolism; sphingolipid metabolism; glycine and serine metabolism; GL metabolism; and tryptophan metabolism with different trends in THP-1 macrophages. However, the impact of both bacterial secretome on arginine and proline metabolism was similar. These data could contribute to a better understanding of pathogenesis and resistance of these bacteria and could pave the way for developing new therapeutics that selectively targeting Gram-positive or Gram-negative bacteria.
{"title":"Treatment of Macrophages with Gram-Negative and -Positive Bacterial Secretomes Induce Distinct Metabolic Signatures","authors":"Alaa Abuawad","doi":"10.35516/jjps.v16i2.1508","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1508","url":null,"abstract":"Infectious diseases represent major health and economic challenges globally. Emergence of multiple drug-resistant bacteria in the community and hospital has become a worldwide concern that requires novel approaches for rapid diagnosis and treatment. Metabolomics approach is a powerful tool providing important chemical information about the cellular phenotype of living systems, and the changes in their metabolic pathways in response to various perturbations. Metabolomics has become an important tool to study host-pathogen interactions and to discover potential novel therapeutic targets. In this study, untargeted LC-MS metabolic profiling was applied to differentiate between the impact of the secretome of the Gram-positive S. aureus SH1000 and Gram-negative P. aeruginosa PAO1 bacterial pathogens on THP-1 macrophages. The results showed that S. aureus and P. aeruginosa secretome affected alanine, aspartate and glutamate metabolism; sphingolipid metabolism; glycine and serine metabolism; GL metabolism; and tryptophan metabolism with different trends in THP-1 macrophages. However, the impact of both bacterial secretome on arginine and proline metabolism was similar. These data could contribute to a better understanding of pathogenesis and resistance of these bacteria and could pave the way for developing new therapeutics that selectively targeting Gram-positive or Gram-negative bacteria.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41325040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1533
Noor Barakat, Mai Jaber, Hatim S Alkhatib
Lowering Intraocular pressure (IOP) is a main therapeutic objective in glaucoma patients because IOP is an important risk factor for glaucoma progression. The objective of this work was to formulate and evaluate, in vitro and in vivo, a stable and effective Solid in Oil (S/O) topical formulation of the antiglaucoma drug, timolol maleate (TM). S/O dispersions were prepared by emulsification of aqueous TM solutions in cyclohexane using different amount of the span 85 then lyophilizing the emulsion to produce TM – Span 85 complexes. The complexes were then dispersed in castor oil using tip sonicator to produce S/O nanodispersions. S/O nanodispersions were evaluated in terms of particle size, polydispersity index, encapsulation efficiency, morphology, physical stability, as well as transcorneal permeation and accumulation of TM. In addition, the in vivo tolerability and efficacy of the prepared formulation in lowering intraocular pressure were evaluated in rabbits. Spherical nanoparticles of TM with a particle size of about 134-155 nm were successfully prepared and found to be physically stable. The encapsulation efficiency was high and was found to be dependent on the level of Span 85 used. In comparison to TM solution, S/O nanodispersion enhanced TM permeation and decreased accumulation in transcorneal diffusion studies. In addition, application TM S/O nanodispersion onto rabbit eyes resulted in a significant reduction in IOP in comparison to TM aqueous solution.
{"title":"Preparation, in vitro and in vivo evaluation of solid-in-oil dispersion-based formulation the anti-glaucoma drug, timolol maleate","authors":"Noor Barakat, Mai Jaber, Hatim S Alkhatib","doi":"10.35516/jjps.v16i2.1533","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1533","url":null,"abstract":"Lowering Intraocular pressure (IOP) is a main therapeutic objective in glaucoma patients because IOP is an important risk factor for glaucoma progression. The objective of this work was to formulate and evaluate, in vitro and in vivo, a stable and effective Solid in Oil (S/O) topical formulation of the antiglaucoma drug, timolol maleate (TM). S/O dispersions were prepared by emulsification of aqueous TM solutions in cyclohexane using different amount of the span 85 then lyophilizing the emulsion to produce TM – Span 85 complexes. The complexes were then dispersed in castor oil using tip sonicator to produce S/O nanodispersions. S/O nanodispersions were evaluated in terms of particle size, polydispersity index, encapsulation efficiency, morphology, physical stability, as well as transcorneal permeation and accumulation of TM. In addition, the in vivo tolerability and efficacy of the prepared formulation in lowering intraocular pressure were evaluated in rabbits. \u0000Spherical nanoparticles of TM with a particle size of about 134-155 nm were successfully prepared and found to be physically stable. The encapsulation efficiency was high and was found to be dependent on the level of Span 85 used. \u0000In comparison to TM solution, S/O nanodispersion enhanced TM permeation and decreased accumulation in transcorneal diffusion studies. In addition, application TM S/O nanodispersion onto rabbit eyes resulted in a significant reduction in IOP in comparison to TM aqueous solution.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44313922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1470
Buthaina Hussein, Laurance M S Bourghli, Muhammed Alzweiri, Y. Al-Hiari, Mohammad Abu Sini, Soraya Alnabulsi, Batool Al-Ghwairi
Fifteen compounds were synthesized and tested as potential carbonic anhydrase III (CAIII) and carbonic anhydrase IX (CAIX) inhibitors, six of which are novel. Amides (a1-4), hydroxamic acids (b1-2), and imines (c1-9) derivatives were evaluated for their inhibitory activity against CAII and CAIX using gas chromatography with modified pH-sensitive pellets. The derivatives showed inhibition percentages between 12-56% for CAIII and 44-59% for CAIX, compared to 49% and 63% for captopril (the positive control), respectively. Imines showed the best inhibition of CAIII, while all derivatives showed comparable activity against CAIX. It is hypothesized that the nitrogen atom in imine, amide, or hydroxamic acid moieties in the vicinity of an ionizable group is in coordination with the zinc ion in the active site. Furthermore, the candidates were tested for their antimicrobial and antifungal activity. Generally, they showed low to zero activity against some gram-positive and negative bacteria. This supports the theory of their ability to bind to human carbonic anhydrase but not to bacterial one. These compounds could serve as useful scaffolds to develop more potent and selective carbonic anhydrase inhibitors as anti-obesity and anticancer candidates.
{"title":"Synthesis and Biological Evaluation of Carbonic Anhydrase III and IX Inhibitors using Gas Chromatography with Modified pH Sensitive Pellets","authors":"Buthaina Hussein, Laurance M S Bourghli, Muhammed Alzweiri, Y. Al-Hiari, Mohammad Abu Sini, Soraya Alnabulsi, Batool Al-Ghwairi","doi":"10.35516/jjps.v16i2.1470","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1470","url":null,"abstract":"Fifteen compounds were synthesized and tested as potential carbonic anhydrase III (CAIII) and carbonic anhydrase IX (CAIX) inhibitors, six of which are novel. Amides (a1-4), hydroxamic acids (b1-2), and imines (c1-9) derivatives were evaluated for their inhibitory activity against CAII and CAIX using gas chromatography with modified pH-sensitive pellets. The derivatives showed inhibition percentages between 12-56% for CAIII and 44-59% for CAIX, compared to 49% and 63% for captopril (the positive control), respectively. Imines showed the best inhibition of CAIII, while all derivatives showed comparable activity against CAIX. It is hypothesized that the nitrogen atom in imine, amide, or hydroxamic acid moieties in the vicinity of an ionizable group is in coordination with the zinc ion in the active site. Furthermore, the candidates were tested for their antimicrobial and antifungal activity. Generally, they showed low to zero activity against some gram-positive and negative bacteria. This supports the theory of their ability to bind to human carbonic anhydrase but not to bacterial one. These compounds could serve as useful scaffolds to develop more potent and selective carbonic anhydrase inhibitors as anti-obesity and anticancer candidates.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42918588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1535
Enas Alqudah, Malak Abbadi, Sawsan Alqadoomi, Ibtihal Abo Hameda, S. Arar, K. Sweidan
A gradient high performance liquid chromatography (HPLC) method has been developed for the qualitative and quantitative analyses of vildagliptin related substances. This method is based on using of RP-C18 (250 × 4.6 mm×5µm) and gradient elution with phosphate buffer and methanol as mobile phase. Various forced degradation studies were conducted to establish an impurity profile for vildagliptin in the tablet formula. Three degradation products were produced upon exposing vildagliptin to different degradation conditions (acidic, basic, oxidative, photolytic, aqueous and thermal); their structures were characterized using LC-MS and NMR (1H NMR, 13C NMR and DEPT) techniques. Some excipient components, examined in this study, had major effect towards producing any extra new degradation products.
{"title":"Identification and Separation of the Degradation Products of Vildagliptin Tablets and Raw Material using LC-MS and NMR, and then Exploration of the Corresponding Degradation Pathways","authors":"Enas Alqudah, Malak Abbadi, Sawsan Alqadoomi, Ibtihal Abo Hameda, S. Arar, K. Sweidan","doi":"10.35516/jjps.v16i2.1535","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1535","url":null,"abstract":"A gradient high performance liquid chromatography (HPLC) method has been developed for the qualitative and quantitative analyses of vildagliptin related substances. This method is based on using of RP-C18 (250 × 4.6 mm×5µm) and gradient elution with phosphate buffer and methanol as mobile phase. Various forced degradation studies were conducted to establish an impurity profile for vildagliptin in the tablet formula. Three degradation products were produced upon exposing vildagliptin to different degradation conditions (acidic, basic, oxidative, photolytic, aqueous and thermal); their structures were characterized using LC-MS and NMR (1H NMR, 13C NMR and DEPT) techniques. Some excipient components, examined in this study, had major effect towards producing any extra new degradation products.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45074463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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