The Experts below are selected from a list of 33822 Experts worldwide ranked by ideXlab platform
Michael P Pollastri - One of the best experts on this subject based on the ideXlab platform.
-
kinase scaffold repurposing for Neglected Disease drug discovery discovery of an efficacious lapatanib derived lead compound for trypanosomiasis
Journal of Medicinal Chemistry, 2013Co-Authors: Gautam Patel, Ranjan Behera, Caitlin E Karver, Paul J Guyett, Catherine Sullenberger, Peter M Edwards, Norma Roncal, Kojo Mensawilmot, Michael P PollastriAbstract:Human African trypanosomiasis (HAT) is a Neglected tropical Disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for Neglected Diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.
-
Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis
2013Co-Authors: Gautam Patel, Ranjan Behera, Kojo Mensa-wilmot, Caitlin E Karver, Paul J Guyett, Catherine Sullenberger, Norma Roncal, Peter Edwards, Michael P PollastriAbstract:Human African trypanosomiasis (HAT) is a Neglected tropical Disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for Neglected Diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle
Ingela Krantz - One of the best experts on this subject based on the ideXlab platform.
-
Editorial Tungiasis—A Neglected Disease with Many Challenges for Global Public Health
2016Co-Authors: Hermann Feldmeier, Uade Samuel Ugbomoiko, Pamela Sabina Mbabazi, Ingela Krantz, Elizabeth Sentongo, Jorg Heukelbach, Georg Von Samson-himmelstjerna, The International ExpertAbstract:Tungiasis (sand flea Disease) is a para-sitic skin Disease with origins in South America. It was introduced into sub-Saharan Africa in the 19th century [1
-
Tungiasis - A Neglected Disease with Many Challenges for Global Public Health
PLOS Neglected Tropical Diseases, 2014Co-Authors: Hermann Feldmeier, Uade Samuel Ugbomoiko, Pamela Sabina Mbabazi, Elizabeth Sentongo, Georg Von Samson-himmelstjerna, Jorg Heukelbach, Ingela KrantzAbstract:Tungiasis (sand flea Disease) is a parasitic skin Disease with origins in South America. It was introduced into sub-Saharan Africa in the 19th century [1]–[3]. Sand flea Disease is a zoonosis caused by the penetration of female sand fleas into the skin. In humans, tungiasis predominantly affects marginalized populations. Children and elderly people are especially susceptible to severe Disease. Sand flea Disease is the most frequent parasitic infection in many resource-poor communities. In animals like dogs, pigs, or ruminants, the infection has severe consequences with, for example, reduced milk production when the skin of the udder is affected. Despite the substantial Disease burden caused by embedded sand fleas, tungiasis is basically Neglected by health care providers, policy makers, the scientific community, the pharmaceutical industry, and funding institutions [4]. Although not included in WHO's list of Neglected tropical Diseases (NTDs), tungiasis bears all the hallmarks of an NTD to merit apprehension from the public health sector [5]–[7]. It occurs in resource-poor communities, causing considerable morbidity and loss of quality of life. Systematic data on Disease occurrence are not available.
Francesca Tamarozzi - One of the best experts on this subject based on the ideXlab platform.
-
cystic echinococcosis of the liver a primer for hepatologists
World Journal of Hepatology, 2014Co-Authors: Francesca Rinaldi, Enrico Brunetti, Andreas Neumayr, Marcello Maestri, Samuel Goblirsch, Francesca TamarozziAbstract:Cystic echinococcosis (CE) is a complex, chronic and Neglected Disease with a worldwide distribution. The liver is the most frequent location of parasitic cysts. In humans, its clinical spectrum ranges from asymptomatic infection to severe, potentially fatal Disease. Four approaches exist in the clinical management of CE: surgery, percutaneous techniques and drug treatment for active cysts, and the "watch and wait" approach for inactive cysts. Allocation of patients to these treatments should be based on cyst stage, size and location, available clinical expertise, and comorbidities. However, clinical decision algorithms, efficacy, relapse rates, and costs have never been properly evaluated. This paper reviews recent advances in classification and diagnosis and the currently available evidence for clinical decision-making in cystic echinococcosis of the liver.
Walderez O Dutra - One of the best experts on this subject based on the ideXlab platform.
-
acute chagas Disease new global challenges for an old Neglected Disease
PLOS Neglected Tropical Diseases, 2014Co-Authors: Daniela V Andrade, Kenneth J Gollob, Walderez O DutraAbstract:Chagas Disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas Disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas Disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the Disease is scarce. In this review, we will discuss (1) the current status of acute Chagas Disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in Disease outcome, and (3) reactivation of Chagas Disease in immunocompromised individuals, a key point for transplantation and HIV infection management.
Hermann Feldmeier - One of the best experts on this subject based on the ideXlab platform.
-
Editorial Tungiasis—A Neglected Disease with Many Challenges for Global Public Health
2016Co-Authors: Hermann Feldmeier, Uade Samuel Ugbomoiko, Pamela Sabina Mbabazi, Ingela Krantz, Elizabeth Sentongo, Jorg Heukelbach, Georg Von Samson-himmelstjerna, The International ExpertAbstract:Tungiasis (sand flea Disease) is a para-sitic skin Disease with origins in South America. It was introduced into sub-Saharan Africa in the 19th century [1
-
Tungiasis - A Neglected Disease with Many Challenges for Global Public Health
PLOS Neglected Tropical Diseases, 2014Co-Authors: Hermann Feldmeier, Uade Samuel Ugbomoiko, Pamela Sabina Mbabazi, Elizabeth Sentongo, Georg Von Samson-himmelstjerna, Jorg Heukelbach, Ingela KrantzAbstract:Tungiasis (sand flea Disease) is a parasitic skin Disease with origins in South America. It was introduced into sub-Saharan Africa in the 19th century [1]–[3]. Sand flea Disease is a zoonosis caused by the penetration of female sand fleas into the skin. In humans, tungiasis predominantly affects marginalized populations. Children and elderly people are especially susceptible to severe Disease. Sand flea Disease is the most frequent parasitic infection in many resource-poor communities. In animals like dogs, pigs, or ruminants, the infection has severe consequences with, for example, reduced milk production when the skin of the udder is affected. Despite the substantial Disease burden caused by embedded sand fleas, tungiasis is basically Neglected by health care providers, policy makers, the scientific community, the pharmaceutical industry, and funding institutions [4]. Although not included in WHO's list of Neglected tropical Diseases (NTDs), tungiasis bears all the hallmarks of an NTD to merit apprehension from the public health sector [5]–[7]. It occurs in resource-poor communities, causing considerable morbidity and loss of quality of life. Systematic data on Disease occurrence are not available.
