alexa Selective inhibitors of Plasmodium falciparum glycogen synthase-3 (PfGSK-3): New antimalarial agents?
Infectious Diseases

Infectious Diseases

Malaria Control & Elimination

Author(s): Masch A, Kunick C

Abstract Share this page

Abstract Plasmodium falciparum glycogen synthase kinase-3 (PfGSK-3) is one of the eukaryotic protein kinases that were identified as essential for the parasite causing malaria tropica. Although the physiological functions of PfGSK-3 are still unknown, it had been suggested as a putative target for novel antimalarial drugs. The high structural similarity of PfGSK-3 and its human orthologue HsGSK-3 makes the development of selective PfGSK-3 inhibitors a challenging task. Actually, established GSK-3 inhibitors are either unselective or are more potent for inhibition of the mammalian GSK-3. A high throughput screening campaign identified thieno[2,3-b]pyridines as a new class of PfGSK-3 inhibitors. Systematic variation of the substitution pattern at the parent scaffold led to compounds which selectively inhibited the plasmodial enzyme. These compounds also exhibited activity against erythrocyte stages of the parasites. A hypothetical explanation for the selectivity of the new antimalarial compounds was enunciated based on the results of docking a selective inhibitor into a PfGSK-3 homology model and by comparison of the results with an X-ray structure of HsGSK-3 co-crystallized with a similar but unselective compound. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases. Copyright © 2015 Elsevier B.V. All rights reserved. This article was published in Biochim Biophys Acta and referenced in Malaria Control & Elimination

Relevant Expert PPTs

Relevant Speaker PPTs

  • Gerald J Prud`homme
    Gamma-aminobutyric acid (GABA) treatment blocks inflammatory pathways and promotes survival and proliferation of pancreatic beta cells
    PPT Version | PDF Version
  • Eva E Avila
    Interaction of the parasite Trichomonas vaginalis with human neutrophil extracellular traps
    PPT Version | PDF Version
  • Rohin Vinayak
    Role of compassion fatigue in quality of life, and marital satisfaction among spouses of patients with diabetes type 2
    PPT Version | PDF Version
  • Saraswathi K
    Diagnosis of different stages of non-proliferative diabetic retinopathy
    PPT Version | PDF Version
  • Zuheir Barsoum
    Zuheir-Barsoum-Khalifa-University-UAE-Life-extension-upgrade-and-repair-of-welded-structures-Towards-the-use-of-High-Strength-Steels
    PPT Version | PDF Version
  • Mikael Bjerg Caspersen
    Innovative albumin based technology for half-life extension and optimization of Biotherapeutics
    PPT Version | PDF Version
  • Isac da Silva Ferreira Lima
    Factors related with early treatment for malaria in the Brazilian Amazon: A multivariable approach using a ten-year population-based malaria surveillance database
    PPT Version | PDF Version
  • Yosef Yarden
    Classically, the 3’untranslated region (3’UTR) is that region in eukaryotic protein-coding genes from the translation termination codon to the polyA signal. It is transcribed as an integral part of the mRNA encoded by the gene. However, there exists another kind of RNA, which consists of the 3’UTR alone, without all other elements in mRNA such as 5’UTR and coding region. The importance of independent 3’UTR RNA (referred as I3’UTR) was prompted by results of artificially introducing such RNA species into malignant mammalian cells. Since 1991, we found that the middle part of the 3’UTR of the human nuclear factor for interleukin-6 (NF-IL6) or C/EBP gene exerted tumor suppression effect in vivo. Our subsequent studies showed that transfection of C/EBP 3’UTR led to down-regulation of several genes favorable for malignancy and to up-regulation of some genes favorable for phenotypic reversion. Also, it was shown that the sequences near the termini of the C/EBP 3’UTR were important for its tumor suppression activity. Then, the C/EBP 3’UTR was found to directly inhibit the phosphorylation activity of protein kinase CPKC in SMMC-7721, a hepatocarcinoma cell line. Recently, an AU-rich region in the C/EBP 3’UTR was found also to be responsible for its tumor suppression. Recently we have also found evidence that the independent C/EBP 3’UTR RNA is actually exists in human tissues, such as fetal liver and heart, pregnant uterus, senescent fibroblasts etc. Through 1990’s to 2000’s, world scientists found several 3’UTR RNAs that functioned as artificial independent RNAs in cancer cells and resulted in tumor suppression. Interestingly, majority of genes for these RNAs have promoter-like structures in their 3’UTR regions, although the existence of their transcribed products as independent 3’UTR RNAs is still to be confirmed. Our studies indicate that the independent 3’UTR RNA is a novel non-coding RNA species whose function should be the regulation not of the expression of their original mRNA, but of some essential life activities of the cell as a whole.
    PPT Version | PDF Version
  • Jihea Choi
    Health-related Quality of Life of Adolescent with Idiopathic Scoliosis in Korea
    PPT Version | PDF Version
  • Raquel García Pacheco
    Evaluation of the ppm-h concept for end-of-life RO membrane into recycled NF and UF membranes
    PPT Version | PDF Version
  • Ana de Guzmán Báez
    Gypsum to Gypsum (GtoG): The European life project that aims to transform the gypsum waste market
    PPT Version | PDF Version
  • Tahany H. Ayaad
    External immune stimulation and its impact on the honey bee Apis mellifera jementica in Saudi Arabia
    PPT Version | PDF Version
  • S Bhuvaneswari
    Effect of packaging film of different thicknesses on shelf life and quality of minimally processed onion
    PPT Version | PDF Version
  • Augustine Okwesil
    Prevalence of Malaria Parasitaemia and methaemoglobin levels among blood donors in Sokoto, Nigeria
    PPT Version | PDF Version
  • Mehmet Saydam
    Quality-of- life, body image and cosmesis after single incision laparoscopic cholecystectomy versus laparoscopic cholecystectomy
    PPT Version | PDF Version
Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

agriaquaculture@omicsonline.com

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

biochemjournals@omicsonline.com

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

business@omicsonline.com

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

chemistryjournals@omicsonline.com

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

clinicaljournals@omicsonline.com

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

engineeringjournals@omicsonline.com

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

nutritionjournals@omicsonline.com

1-702-714-7001Extn: 9042

General Science

Andrea Jason

generalscience@omicsonline.com

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

geneticsmolbio@omicsonline.com

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

immunomicrobiol@omicsonline.com

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

materialsci@omicsonline.com

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

nursinghealthcare@omicsonline.com

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

medicaljournals@omicsonline.com

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

neuropsychology@omicsonline.com

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

pharmajournals@omicsonline.com

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

social_politicalsci@omicsonline.com

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords