Abstract:
:We recently reported the medicinal chemistry re-optimization of a series of compounds derived from the human tyrosine kinase inhibitor, lapatinib, for activity against Plasmodium falciparum. From this same library of compounds, we now report potent compounds against Trypanosoma brucei brucei (which causes human African trypanosomiasis), T. cruzi (the pathogen that causes Chagas disease), and Leishmania spp. (which cause leishmaniasis). In addition, sub-micromolar compounds were identified that inhibit proliferation of the parasites that cause African animal trypanosomiasis, T. congolense and T. vivax. We have found that this set of compounds display acceptable physicochemical properties and represent progress towards identification of lead compounds to combat several neglected tropical diseases.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Ferrins L,Sharma A,Thomas SM,Mehta N,Erath J,Tanghe S,Leed SE,Rodriguez A,Mensa-Wilmot K,Sciotti RJ,Gillingwater K,Pollastri MPdoi
10.1371/journal.pntd.0006834subject
Has Abstractpub_date
2018-11-26 00:00:00pages
e0006834issue
11eissn
1935-2727issn
1935-2735pii
PNTD-D-18-00885journal_volume
12pub_type
杂志文章abstract:INTRODUCTION:Plasmodium knowlesi is now recognised as a leading cause of malaria in Malaysia. As humans come into increasing contact with the reservoir host (long-tailed macaques) as a consequence of deforestation, assessing the potential for a shift from zoonotic to sustained P. knowlesi transmission between humans is...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002978
更新日期:2014-07-24 00:00:00
abstract:BACKGROUND:Dengue is a serious vector-borne disease, and incidence rates have significantly increased during the past few years, particularly in 2014 in Guangzhou. The current situation is more complicated, due to various factors such as climate warming, urbanization, population increase, and human mobility. The purpos...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004633
更新日期:2016-04-22 00:00:00
abstract::Leprosy is a persistent infectious disease caused by Mycobacterium leprae that still affects over 200,000 new patients annually. The host genetic background is an important risk factor for leprosy susceptibility and the PARK2 gene is a replicated leprosy susceptibility candidate gene. The protein product of PARK2, Par...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002015
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Resistance emergence against antileishmanial drugs, particularly Sodium Antimony Gluconate (SAG) has severely hampered the therapeutic strategy against visceral leishmaniasis, the mechanism of resistance being indistinguishable. Cysteine leucine rich protein (CLrP), was recognized as one of the overexpressed...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003992
更新日期:2015-08-21 00:00:00
abstract::Burkholderia pseudomallei, the bacterial agent of melioidosis, causes disease through inhalation of infectious particles, and is classified as a Tier 1 Select Agent. Optical diagnostic imaging has demonstrated that murine respiratory disease models are subject to significant upper respiratory tract (URT) colonization....
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003441
更新日期:2015-01-08 00:00:00
abstract::ELISA-based methods of detecting Fasciola cathepsins in feces are powerful techniques for diagnosing infections by F. hepatica and F. gigantica. In the last decade, the in-house MM3-COPRO ELISA and its commercial version BIO K 201 (BIO X Diagnostics, Belgium) have been recognized as useful tools for detecting early in...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004872
更新日期:2016-07-20 00:00:00
abstract:BACKGROUND:Opisthorchis felineus, O. viverrini, and Clonorchis sinensis (family Opisthorchiidae) are parasitic flatworms that pose a serious threat to humans in some countries and cause opisthorchiasis/clonorchiasis. Chronic disease may lead to a risk of carcinogenesis in the biliary ducts. MicroRNAs (miRNAs) are small...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003680
更新日期:2015-04-21 00:00:00
abstract::The agents of sleeping sickness disease, Trypanosoma brucei complex parasites, are transmitted to mammalian hosts through the bite of an infected tsetse. Information on tsetse-trypanosome interactions in the salivary gland (SG) tissue, and on mammalian infective metacyclic (MC) parasites present in the SG, is sparse. ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002649
更新日期:2014-04-24 00:00:00
abstract:BACKGROUND:Junín virus (JUNV), the etiologic agent of Argentine hemorrhagic fever (AHF), is classified by the NIAID and CDC as a Category A priority pathogen. Presently, antiviral therapy for AHF is limited to immune plasma, which is readily available only in the endemic regions of Argentina. T-705 (favipiravir) is a b...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002614
更新日期:2013-12-26 00:00:00
abstract:AUTHOR SUMMARY:Designing and implementing effective programs for infectious disease control requires complex decision-making, informed by an understanding of the diseases, the types of disease interventions and control measures available, and the disease-relevant characteristics of the local community. Though disease m...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006328
更新日期:2018-04-12 00:00:00
abstract:BACKGROUND:Marburg virus (MARV), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever (MHF) with the highest case fatality rate to date. METHODOLOGY/PRINCIPAL FINDINGS:A mobile laboratory unit (MLU) was deployed as part of the...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001183
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND:The factors influencing variation in the clinical forms of Chagas disease have not been elucidated; however, it is likely that the genetics of both the host and the parasite are involved. Several studies have attempted to correlate the T. cruzi strains involved in infection with the clinical forms of the dis...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002524
更新日期:2013-10-31 00:00:00
abstract::Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social sti...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003405
更新日期:2014-12-18 00:00:00
abstract:INTRODUCTION:Plasmodium spp. and helminths are co-endemic in many parts of the tropics; hence, co-infection is a common phenomenon. Interactions between Plasmodium and helminth infections may alter the host's immune response and susceptibility and thus impact on morbidity. There is little information on the direction a...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007086
更新日期:2019-01-10 00:00:00
abstract::A 51-year-old man with 3-month unhealing cat bite wound was diagnosed with sporotrichosis, a subacute-to-chronic infection caused by the worldwide endemic, dimorphic fungus Sporothrix globosa. The case would help clinicians to raise awareness of human sporotrichosis due to cat bites, which remains rare and is likely t...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008859
更新日期:2020-12-03 00:00:00
abstract::Canine rabies was endemic pre-urbanisation, yet little is known about how it persists in small populations of dogs typically seen in rural and remote regions. By simulating rabies outbreaks in such populations (50-90 dogs) using a network-based model, our objective was to determine if rabies-induced behavioural change...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007739
更新日期:2019-09-23 00:00:00
abstract::Tsetse flies (Glossina spp.) transmit parasitic African trypanosomes (Trypanosoma spp.), including Trypanosoma congolense, which causes animal African trypanosomiasis (AAT). AAT detrimentally affects agricultural activities in sub-Saharan Africa and has negative impacts on the livelihood and nutrient availability for ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006057
更新日期:2017-11-20 00:00:00
abstract:BACKGROUND:The clinical syndrome associated with secondary syphilis (SS) reflects the propensity of Treponema pallidum (Tp) to escape immune recognition while simultaneously inducing inflammation. METHODS:To better understand the duality of immune evasion and immune recognition in human syphilis, herein we used a comb...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001717
更新日期:2012-01-01 00:00:00
abstract::We briefly review cysteine proteases (orthologs of mammalian cathepsins B, L, F, and C) that are expressed in flatworm and nematode parasites. Emphasis is placed on enzyme activities that have been functionally characterized, are associated with the parasite gut, and putatively contribute to degrading host proteins to...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0005840
更新日期:2018-08-23 00:00:00
abstract:BACKGROUND:Current WHO recommendations for lymphatic filariasis (LF) surveillance advise programs to implement activities to monitor for new foci of transmission after stopping mass drug administration (MDA). A current need in the global effort to eliminate LF is to standardize diagnostic tools and surveillance activit...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006347
更新日期:2018-03-09 00:00:00
abstract::P. vivax and P. falciparum parasites display different tropism for host cells and induce very different clinical symptoms and pathology, suggesting that the immune responses required for protection may differ between these two species. However, no study has qualitatively compared the immune responses to P. falciparum ...
journal_title:PLoS neglected tropical diseases
pub_type: 临床试验,杂志文章
doi:10.1371/journal.pntd.0005031
更新日期:2016-12-08 00:00:00
abstract:BACKGROUND:In 2007, a novel bunyavirus was found in Henan Province, China and named fever, thrombocytopenia and leukocytopenia syndrome virus (FTLSV); since then, FTLSV has been found in ticks and animals in many Chinese provinces. Human-to-human transmission has been documented, indicating that FTLSV should be conside...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003237
更新日期:2014-10-16 00:00:00
abstract:BACKGROUND:Taenia solium cysticercosis affects millions of impoverished people worldwide and can cause neurocysticercosis, an infection of the central nervous system which is potentially fatal. Children may represent an especially vulnerable population to neurocysticercosis, due to the risk of cognitive impairment duri...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006465
更新日期:2018-05-08 00:00:00
abstract::The Leishmania genus comprises up to 35 species, some with status still under discussion. The multilocus sequence typing (MLST)--extensively used for bacteria--has been proposed for pathogenic trypanosomatids. For Leishmania, however, a detailed analysis and revision on the taxonomy is still required. We have partiall...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001888
更新日期:2012-01-01 00:00:00
abstract::Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative bacillus, primarily found in soils in Southeast Asia and northern Australia. A recent case of melioidosis in non-endemic Arizona was determined to be the result of locally acquired infection, as the patient had no travel history to endemic regions and...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001347
更新日期:2011-10-01 00:00:00
abstract::Japanese encephalitis (JE) is the leading form of viral encephalitis in Asia. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. JEV is endemic to many parts of Asia, where periodic outbreaks take hundreds of lives. Despite the catastrophes it causes, JE has remained a tropical disease uncom...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000437
更新日期:2009-09-29 00:00:00
abstract:BACKGROUND:Area-wide integrated pest management strategies that include a sterile insect technique component have been successfully used to eradicate tsetse fly populations in the past. To ensure the success of the sterile insect technique, the released males must be adequately sterile and be able to compete with their...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005473
更新日期:2017-03-17 00:00:00
abstract::Mosquito-borne chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus from the genus Alphavirus, family Togaviridae, which causes fever, rash and severe persistent polyarthralgia in humans. Since there are currently no FDA licensed vaccines or antiviral therapies for CHIKV, the development of vaccine...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002719
更新日期:2014-02-20 00:00:00
abstract::Schistosomiasis control and elimination has priority in public health agendas in several sub-Saharan countries. However, achieving these goals remains a substantial challenge. In order to assess progress of interventions and treatment efficacy it is pertinent to have accurate, feasible and affordable diagnostic tools....
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,随机对照试验
doi:10.1371/journal.pntd.0006054
更新日期:2017-11-13 00:00:00
abstract::The infectious form of many parasitic nematodes, which afflict over one billion people globally, is a developmentally arrested third-stage larva (L3i). The parasitic nematode Strongyloides stercoralis differs from other nematode species that infect humans, in that its life cycle includes both parasitic and free-living...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001854
更新日期:2012-01-01 00:00:00