Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding between <i>Plasmodium falciparum</i> Infected Erythrocytes and Endothelial Receptor ICAM-1
Specific adhesion of <i>P. falciparum</i> parasite-infected erythrocytes (IE) in deep vascular beds can result in severe complications, such as cerebral malaria, placental malaria, respiratory distress, and severe anemia. Cerebral malaria and severe malaria syndromes were associated prev...
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MDPI AG
2021-05-01
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Series: | International Journal of Molecular Sciences |
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author | Olga Chesnokov Pimnitah Visitdesotrakul Komal Kalani Adel Nefzi Andrew V. Oleinikov |
author_facet | Olga Chesnokov Pimnitah Visitdesotrakul Komal Kalani Adel Nefzi Andrew V. Oleinikov |
author_sort | Olga Chesnokov |
collection | DOAJ |
description | Specific adhesion of <i>P. falciparum</i> parasite-infected erythrocytes (IE) in deep vascular beds can result in severe complications, such as cerebral malaria, placental malaria, respiratory distress, and severe anemia. Cerebral malaria and severe malaria syndromes were associated previously with sequestration of IE to a microvasculature receptor ICAM-1. The screening of Torrey Pines Scaffold Ranking library, which consists of more than 30 million compounds designed around 75 molecular scaffolds, identified small molecules that inhibit cytoadhesion of ICAM-1-binding IE to surface-immobilized receptor at IC<sub>50</sub> range down to ~350 nM. With their low cytotoxicity toward erythrocytes and human endothelial cells, these molecules might be suitable for development into potentially effective adjunct anti-adhesion drugs to treat cerebral and/or severe malaria syndromes. Our two-step high-throughput screening approach is specifically designed to work with compound mixtures to make screening and deconvolution to single active compounds fast and efficient. |
first_indexed | 2024-03-10T11:01:16Z |
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institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T11:01:16Z |
publishDate | 2021-05-01 |
publisher | MDPI AG |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-2e5b83876cd04bfca4abee96b3436e092023-11-21T21:27:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211565910.3390/ijms22115659Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding between <i>Plasmodium falciparum</i> Infected Erythrocytes and Endothelial Receptor ICAM-1Olga Chesnokov0Pimnitah Visitdesotrakul1Komal Kalani2Adel Nefzi3Andrew V. Oleinikov4Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33428, USACharles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33428, USACenter for Translational Science, Florida International University (FIU), Port Saint Lucie, FL 34987, USACenter for Translational Science, Florida International University (FIU), Port Saint Lucie, FL 34987, USACharles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33428, USASpecific adhesion of <i>P. falciparum</i> parasite-infected erythrocytes (IE) in deep vascular beds can result in severe complications, such as cerebral malaria, placental malaria, respiratory distress, and severe anemia. Cerebral malaria and severe malaria syndromes were associated previously with sequestration of IE to a microvasculature receptor ICAM-1. The screening of Torrey Pines Scaffold Ranking library, which consists of more than 30 million compounds designed around 75 molecular scaffolds, identified small molecules that inhibit cytoadhesion of ICAM-1-binding IE to surface-immobilized receptor at IC<sub>50</sub> range down to ~350 nM. With their low cytotoxicity toward erythrocytes and human endothelial cells, these molecules might be suitable for development into potentially effective adjunct anti-adhesion drugs to treat cerebral and/or severe malaria syndromes. Our two-step high-throughput screening approach is specifically designed to work with compound mixtures to make screening and deconvolution to single active compounds fast and efficient.https://www.mdpi.com/1422-0067/22/11/5659<i>P. falciparum</i>severe and cerebral malariasmall molecule inhibitorscombinatorial chemistrymixture-based librariesdrug discovery |
spellingShingle | Olga Chesnokov Pimnitah Visitdesotrakul Komal Kalani Adel Nefzi Andrew V. Oleinikov Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding between <i>Plasmodium falciparum</i> Infected Erythrocytes and Endothelial Receptor ICAM-1 International Journal of Molecular Sciences <i>P. falciparum</i> severe and cerebral malaria small molecule inhibitors combinatorial chemistry mixture-based libraries drug discovery |
title | Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding between <i>Plasmodium falciparum</i> Infected Erythrocytes and Endothelial Receptor ICAM-1 |
title_full | Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding between <i>Plasmodium falciparum</i> Infected Erythrocytes and Endothelial Receptor ICAM-1 |
title_fullStr | Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding between <i>Plasmodium falciparum</i> Infected Erythrocytes and Endothelial Receptor ICAM-1 |
title_full_unstemmed | Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding between <i>Plasmodium falciparum</i> Infected Erythrocytes and Endothelial Receptor ICAM-1 |
title_short | Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding between <i>Plasmodium falciparum</i> Infected Erythrocytes and Endothelial Receptor ICAM-1 |
title_sort | small molecule compounds identified from mixture based library inhibit binding between i plasmodium falciparum i infected erythrocytes and endothelial receptor icam 1 |
topic | <i>P. falciparum</i> severe and cerebral malaria small molecule inhibitors combinatorial chemistry mixture-based libraries drug discovery |
url | https://www.mdpi.com/1422-0067/22/11/5659 |
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