The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Ruqaiyyah Siddiqui - One of the best experts on this subject based on the ideXlab platform.
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potential application of vaporized drugs via nasal inhalers to prevent mortality and central nervous system damage caused by Primary Amoebic Meningoencephalitis due to naegleria fowleri
ACS Pharmacology & Translational Science, 2021Co-Authors: Ruqaiyyah Siddiqui, Mohamed Abouleish, Mustafa Khamis, Taleb H Ibrahim, Naveed Ahmed KhanAbstract:Here, it is proposed that nasal inhalers with specific anti-Naegleria fowleri drugs or a combination of anti-N. fowleri compounds combined with steroids such as dexamethasone could provide a practical solution for treating Primary Amoebic Meningoencephalitis.
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repositioning of guanabenz in conjugation with gold and silver nanoparticles against pathogenic amoebae acanthamoeba castellanii and naegleria fowleri
ACS Infectious Diseases, 2019Co-Authors: Areeba Anwar, Naveed Ahmed Khan, Mohammad Ridwane Mungroo, Ayaz Anwar, William Sullivan, Ruqaiyyah SiddiquiAbstract:Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous Amoebic encephalitis and Primary Amoebic Meningoencephalitis caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiAmoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by the one-phase reduction method and were characterized by ultraviolet–visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz, which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas silver nanoparticles were produced in a larger size ...
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brain eating amoebae silver nanoparticle conjugation enhanced efficacy of anti Amoebic drugs against naegleria fowleri
ACS Chemical Neuroscience, 2017Co-Authors: Kavitha Rajendran, Ayaz Anwar, Naveed Ahmed Khan, Ruqaiyyah SiddiquiAbstract:The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against Primary Amoebic Meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV–visible spectrophotometry. Atomic force microscopy determined their size in range of 20–100 nm. To determine Amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiAmoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiAmoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying exis...
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biology and pathogenesis of naegleria fowleri
Acta Tropica, 2016Co-Authors: Ruqaiyyah Siddiqui, Jennifer R Cope, Naveed Ahmed KhanAbstract:Abstract Naegleria fowleri is a protist pathogen that can cause lethal brain infection. Despite decades of research, the mortality rate related with Primary Amoebic Meningoencephalitis owing to N. fowleri remains more than 90%. The amoebae pass through the nose to enter the central nervous system killing the host within days, making it one of the deadliest opportunistic parasites. Accordingly, we present an up to date review of the biology and pathogenesis of N. fowleri and discuss needs for future research against this fatal infection.
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Primary Amoebic Meningoencephalitis caused by naegleria fowleri an old enemy presenting new challenges
PLOS Neglected Tropical Diseases, 2014Co-Authors: Ruqaiyyah Siddiqui, Naveed Ahmed KhanAbstract:First discovered in 1899, Naegleria fowleri is a protist pathogen, known to infect the central nervous system and produce Primary Amoebic Meningoencephalitis. The most distressing aspect is that the fatality rate has remained more than 95%, despite our advances in antimicrobial chemotherapy and supportive care. Although rare worldwide, most cases have been reported in the United States, Australia, and Europe (France). A large number of cases in developing countries go unnoticed. In particular, religious, recreational, and cultural practices such as ritual ablution and/or purifications, Ayurveda, and the use of neti pots for nasal irrigation can contribute to this devastating infection. With increasing water scarcity and public reliance on water storage, here we debate the need for increased awareness of Primary Amoebic Meningoencephalitis and the associated risk factors, particularly in developing countries.
Naveed Ahmed Khan - One of the best experts on this subject based on the ideXlab platform.
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potential application of vaporized drugs via nasal inhalers to prevent mortality and central nervous system damage caused by Primary Amoebic Meningoencephalitis due to naegleria fowleri
ACS Pharmacology & Translational Science, 2021Co-Authors: Ruqaiyyah Siddiqui, Mohamed Abouleish, Mustafa Khamis, Taleb H Ibrahim, Naveed Ahmed KhanAbstract:Here, it is proposed that nasal inhalers with specific anti-Naegleria fowleri drugs or a combination of anti-N. fowleri compounds combined with steroids such as dexamethasone could provide a practical solution for treating Primary Amoebic Meningoencephalitis.
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repositioning of guanabenz in conjugation with gold and silver nanoparticles against pathogenic amoebae acanthamoeba castellanii and naegleria fowleri
ACS Infectious Diseases, 2019Co-Authors: Areeba Anwar, Naveed Ahmed Khan, Mohammad Ridwane Mungroo, Ayaz Anwar, William Sullivan, Ruqaiyyah SiddiquiAbstract:Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous Amoebic encephalitis and Primary Amoebic Meningoencephalitis caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiAmoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by the one-phase reduction method and were characterized by ultraviolet–visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz, which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas silver nanoparticles were produced in a larger size ...
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brain eating amoebae silver nanoparticle conjugation enhanced efficacy of anti Amoebic drugs against naegleria fowleri
ACS Chemical Neuroscience, 2017Co-Authors: Kavitha Rajendran, Ayaz Anwar, Naveed Ahmed Khan, Ruqaiyyah SiddiquiAbstract:The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against Primary Amoebic Meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV–visible spectrophotometry. Atomic force microscopy determined their size in range of 20–100 nm. To determine Amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiAmoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiAmoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying exis...
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biology and pathogenesis of naegleria fowleri
Acta Tropica, 2016Co-Authors: Ruqaiyyah Siddiqui, Jennifer R Cope, Naveed Ahmed KhanAbstract:Abstract Naegleria fowleri is a protist pathogen that can cause lethal brain infection. Despite decades of research, the mortality rate related with Primary Amoebic Meningoencephalitis owing to N. fowleri remains more than 90%. The amoebae pass through the nose to enter the central nervous system killing the host within days, making it one of the deadliest opportunistic parasites. Accordingly, we present an up to date review of the biology and pathogenesis of N. fowleri and discuss needs for future research against this fatal infection.
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Primary Amoebic Meningoencephalitis caused by naegleria fowleri an old enemy presenting new challenges
PLOS Neglected Tropical Diseases, 2014Co-Authors: Ruqaiyyah Siddiqui, Naveed Ahmed KhanAbstract:First discovered in 1899, Naegleria fowleri is a protist pathogen, known to infect the central nervous system and produce Primary Amoebic Meningoencephalitis. The most distressing aspect is that the fatality rate has remained more than 95%, despite our advances in antimicrobial chemotherapy and supportive care. Although rare worldwide, most cases have been reported in the United States, Australia, and Europe (France). A large number of cases in developing countries go unnoticed. In particular, religious, recreational, and cultural practices such as ritual ablution and/or purifications, Ayurveda, and the use of neti pots for nasal irrigation can contribute to this devastating infection. With increasing water scarcity and public reliance on water storage, here we debate the need for increased awareness of Primary Amoebic Meningoencephalitis and the associated risk factors, particularly in developing countries.
Ruben Abagyan - One of the best experts on this subject based on the ideXlab platform.
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identification of four Amoebicidal nontoxic compounds by a molecular docking screen of naegleria fowleri sterol δ8 δ7 isomerase and phenotypic assays
ACS Infectious Diseases, 2019Co-Authors: Kirti Kandhwal Chahal, Louisfelix Nothias, Anjan Debnath, Larissa M Podust, James H Mckerrow, Ruben AbagyanAbstract:Naegleria fowleri is a free-living amoeba causing Primary Amoebic Meningoencephalitis, a rapid-onset brain infection in humans with over 97% mortality rate. Despite some progress in the treatment of the disease, there is no single, proven, evidence-based treatment with a high probability of cure. Here we report the chemical library screening and experimental identification of four new compounds with Amoebicidal effects against N. fowleri. The chemical library was screened by molecular docking against a homology model of sterol Δ8−Δ7 isomerase (NfERG2). Thirty top-ranking hits were then tested in a cell-based assay for antiproliferative/Amoebicidal activities. Eight chemicals exhibited nearly 100% inhibition of N. fowleri at 50 μM, with the EC50 values ranging from 6 to 25 μM. A cell toxicity assay using human HEK-293 cells was also performed. Four of the compounds preferentially kill amoeba cells with no apparent human cell toxicities. These compounds fall into two distinct chemical scaffolds with druglik...
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identification of four Amoebicidal nontoxic compounds by a molecular docking screen of naegleria fowleri sterol δ8 δ7 isomerase and phenotypic assays
ACS Infectious Diseases, 2019Co-Authors: Da Shi, Kirti Kandhwal Chahal, Louisfelix Nothias, Anjan Debnath, Larissa M Podust, James H Mckerrow, Patricia Oto, Ruben AbagyanAbstract:Naegleria fowleri is a free-living amoeba causing Primary Amoebic Meningoencephalitis, a rapid-onset brain infection in humans with over 97% mortality rate. Despite some progress in the treatment of the disease, there is no single, proven, evidence-based treatment with a high probability of cure. Here we report the chemical library screening and experimental identification of four new compounds with Amoebicidal effects against N. fowleri. The chemical library was screened by molecular docking against a homology model of sterol Δ8-Δ7 isomerase (NfERG2). Thirty top-ranking hits were then tested in a cell-based assay for antiproliferative/Amoebicidal activities. Eight chemicals exhibited nearly 100% inhibition of N. fowleri at 50 μM, with the EC50 values ranging from 6 to 25 μM. A cell toxicity assay using human HEK-293 cells was also performed. Four of the compounds preferentially kill amoeba cells with no apparent human cell toxicities. These compounds fall into two distinct chemical scaffolds with druglike properties.
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cyp51 is an essential drug target for the treatment of Primary Amoebic Meningoencephalitis pam
PLOS Neglected Tropical Diseases, 2017Co-Authors: Anjan Debnath, Ruben Abagyan, Claudia M Calvet, Gareth K Jennings, Wenxu Zhou, Alexander A Aksenov, Madeline R Luth, W D Nes, James H MckerrowAbstract:Primary Amoebic Meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported) the high mortality rate and lack of established success in treatment makes PAM a particularly devastating infection. In the absence of economic inducements to invest in development of anti-PAM drugs by the pharmaceutical industry, anti-PAM drug discovery largely relies on drug 'repurposing'-a cost effective strategy to apply known drugs for treatment of rare or neglected diseases. Similar to fungi, N. fowleri has an essential requirement for ergosterol, a building block of plasma and cell membranes. Disruption of sterol biosynthesis by small-molecule inhibitors is a validated interventional strategy against fungal pathogens of medical and agricultural importance. The N. fowleri genome encodes the sterol 14-demethylase (CYP51) target sharing ~35% sequence identity to fungal orthologues. The similarity of targets raises the possibility of repurposing anti-mycotic drugs and optimization of their usage for the treatment of PAM. In this work, we (i) systematically assessed the impact of anti-fungal azole drugs, known as conazoles, on sterol biosynthesis and viability of cultured N. fowleri trophozotes, (ii) identified the endogenous CYP51 substrate by mass spectrometry analysis of N. fowleri lipids, and (iii) analyzed the interactions between the recombinant CYP51 target and conazoles by UV-vis spectroscopy and x-ray crystallography. Collectively, the target-based and parasite-based data obtained in these studies validated CYP51 as a potentially 'druggable' target in N. fowleri, and conazole drugs as the candidates for assessment in the animal model of PAM.
James H Mckerrow - One of the best experts on this subject based on the ideXlab platform.
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identification of four Amoebicidal nontoxic compounds by a molecular docking screen of naegleria fowleri sterol δ8 δ7 isomerase and phenotypic assays
ACS Infectious Diseases, 2019Co-Authors: Kirti Kandhwal Chahal, Louisfelix Nothias, Anjan Debnath, Larissa M Podust, James H Mckerrow, Ruben AbagyanAbstract:Naegleria fowleri is a free-living amoeba causing Primary Amoebic Meningoencephalitis, a rapid-onset brain infection in humans with over 97% mortality rate. Despite some progress in the treatment of the disease, there is no single, proven, evidence-based treatment with a high probability of cure. Here we report the chemical library screening and experimental identification of four new compounds with Amoebicidal effects against N. fowleri. The chemical library was screened by molecular docking against a homology model of sterol Δ8−Δ7 isomerase (NfERG2). Thirty top-ranking hits were then tested in a cell-based assay for antiproliferative/Amoebicidal activities. Eight chemicals exhibited nearly 100% inhibition of N. fowleri at 50 μM, with the EC50 values ranging from 6 to 25 μM. A cell toxicity assay using human HEK-293 cells was also performed. Four of the compounds preferentially kill amoeba cells with no apparent human cell toxicities. These compounds fall into two distinct chemical scaffolds with druglik...
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identification of four Amoebicidal nontoxic compounds by a molecular docking screen of naegleria fowleri sterol δ8 δ7 isomerase and phenotypic assays
ACS Infectious Diseases, 2019Co-Authors: Da Shi, Kirti Kandhwal Chahal, Louisfelix Nothias, Anjan Debnath, Larissa M Podust, James H Mckerrow, Patricia Oto, Ruben AbagyanAbstract:Naegleria fowleri is a free-living amoeba causing Primary Amoebic Meningoencephalitis, a rapid-onset brain infection in humans with over 97% mortality rate. Despite some progress in the treatment of the disease, there is no single, proven, evidence-based treatment with a high probability of cure. Here we report the chemical library screening and experimental identification of four new compounds with Amoebicidal effects against N. fowleri. The chemical library was screened by molecular docking against a homology model of sterol Δ8-Δ7 isomerase (NfERG2). Thirty top-ranking hits were then tested in a cell-based assay for antiproliferative/Amoebicidal activities. Eight chemicals exhibited nearly 100% inhibition of N. fowleri at 50 μM, with the EC50 values ranging from 6 to 25 μM. A cell toxicity assay using human HEK-293 cells was also performed. Four of the compounds preferentially kill amoeba cells with no apparent human cell toxicities. These compounds fall into two distinct chemical scaffolds with druglike properties.
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cyp51 is an essential drug target for the treatment of Primary Amoebic Meningoencephalitis pam
PLOS Neglected Tropical Diseases, 2017Co-Authors: Anjan Debnath, Ruben Abagyan, Claudia M Calvet, Gareth K Jennings, Wenxu Zhou, Alexander A Aksenov, Madeline R Luth, W D Nes, James H MckerrowAbstract:Primary Amoebic Meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported) the high mortality rate and lack of established success in treatment makes PAM a particularly devastating infection. In the absence of economic inducements to invest in development of anti-PAM drugs by the pharmaceutical industry, anti-PAM drug discovery largely relies on drug 'repurposing'-a cost effective strategy to apply known drugs for treatment of rare or neglected diseases. Similar to fungi, N. fowleri has an essential requirement for ergosterol, a building block of plasma and cell membranes. Disruption of sterol biosynthesis by small-molecule inhibitors is a validated interventional strategy against fungal pathogens of medical and agricultural importance. The N. fowleri genome encodes the sterol 14-demethylase (CYP51) target sharing ~35% sequence identity to fungal orthologues. The similarity of targets raises the possibility of repurposing anti-mycotic drugs and optimization of their usage for the treatment of PAM. In this work, we (i) systematically assessed the impact of anti-fungal azole drugs, known as conazoles, on sterol biosynthesis and viability of cultured N. fowleri trophozotes, (ii) identified the endogenous CYP51 substrate by mass spectrometry analysis of N. fowleri lipids, and (iii) analyzed the interactions between the recombinant CYP51 target and conazoles by UV-vis spectroscopy and x-ray crystallography. Collectively, the target-based and parasite-based data obtained in these studies validated CYP51 as a potentially 'druggable' target in N. fowleri, and conazole drugs as the candidates for assessment in the animal model of PAM.
Kirti Kandhwal Chahal - One of the best experts on this subject based on the ideXlab platform.
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identification of four Amoebicidal nontoxic compounds by a molecular docking screen of naegleria fowleri sterol δ8 δ7 isomerase and phenotypic assays
ACS Infectious Diseases, 2019Co-Authors: Kirti Kandhwal Chahal, Louisfelix Nothias, Anjan Debnath, Larissa M Podust, James H Mckerrow, Ruben AbagyanAbstract:Naegleria fowleri is a free-living amoeba causing Primary Amoebic Meningoencephalitis, a rapid-onset brain infection in humans with over 97% mortality rate. Despite some progress in the treatment of the disease, there is no single, proven, evidence-based treatment with a high probability of cure. Here we report the chemical library screening and experimental identification of four new compounds with Amoebicidal effects against N. fowleri. The chemical library was screened by molecular docking against a homology model of sterol Δ8−Δ7 isomerase (NfERG2). Thirty top-ranking hits were then tested in a cell-based assay for antiproliferative/Amoebicidal activities. Eight chemicals exhibited nearly 100% inhibition of N. fowleri at 50 μM, with the EC50 values ranging from 6 to 25 μM. A cell toxicity assay using human HEK-293 cells was also performed. Four of the compounds preferentially kill amoeba cells with no apparent human cell toxicities. These compounds fall into two distinct chemical scaffolds with druglik...
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identification of four Amoebicidal nontoxic compounds by a molecular docking screen of naegleria fowleri sterol δ8 δ7 isomerase and phenotypic assays
ACS Infectious Diseases, 2019Co-Authors: Da Shi, Kirti Kandhwal Chahal, Louisfelix Nothias, Anjan Debnath, Larissa M Podust, James H Mckerrow, Patricia Oto, Ruben AbagyanAbstract:Naegleria fowleri is a free-living amoeba causing Primary Amoebic Meningoencephalitis, a rapid-onset brain infection in humans with over 97% mortality rate. Despite some progress in the treatment of the disease, there is no single, proven, evidence-based treatment with a high probability of cure. Here we report the chemical library screening and experimental identification of four new compounds with Amoebicidal effects against N. fowleri. The chemical library was screened by molecular docking against a homology model of sterol Δ8-Δ7 isomerase (NfERG2). Thirty top-ranking hits were then tested in a cell-based assay for antiproliferative/Amoebicidal activities. Eight chemicals exhibited nearly 100% inhibition of N. fowleri at 50 μM, with the EC50 values ranging from 6 to 25 μM. A cell toxicity assay using human HEK-293 cells was also performed. Four of the compounds preferentially kill amoeba cells with no apparent human cell toxicities. These compounds fall into two distinct chemical scaffolds with druglike properties.
