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Novel Baicalein-Derived Inhibitors of Plasmodium falciparum

Malaria, a life-threatening mosquito-borne disease caused by Plasmodium parasites, continues to pose a significant global health burden. Despite notable progress in combating the disease in recent years, malaria remains prevalent in many regions, particularly in Southeast Asia and most of sub-Sahara...

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Autores principales: Gudla, Chandra Sekhar, Selvam, Vignesh, Selvaraj, Siva Shanmugam, Tripathi, Renu, Joshi, Prince, Shaham, Salique Hassan, Singh, Mayas, Shandil, Radha Krishan, Habib, Saman, Narayanan, Shridhar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610289/
https://www.ncbi.nlm.nih.gov/pubmed/37887758
http://dx.doi.org/10.3390/pathogens12101242
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author Gudla, Chandra Sekhar
Selvam, Vignesh
Selvaraj, Siva Shanmugam
Tripathi, Renu
Joshi, Prince
Shaham, Salique Hassan
Singh, Mayas
Shandil, Radha Krishan
Habib, Saman
Narayanan, Shridhar
author_facet Gudla, Chandra Sekhar
Selvam, Vignesh
Selvaraj, Siva Shanmugam
Tripathi, Renu
Joshi, Prince
Shaham, Salique Hassan
Singh, Mayas
Shandil, Radha Krishan
Habib, Saman
Narayanan, Shridhar
author_sort Gudla, Chandra Sekhar
collection PubMed
description Malaria, a life-threatening mosquito-borne disease caused by Plasmodium parasites, continues to pose a significant global health burden. Despite notable progress in combating the disease in recent years, malaria remains prevalent in many regions, particularly in Southeast Asia and most of sub-Saharan Africa, where it claims hundreds of thousands of lives annually. Flavonoids, such as the baicalein class of compounds, are known to have antimalarial properties. In this study, we rationally designed and synthesized a series of baicalein derivatives and identified a lead compound, FNDR-10132, that displayed potent in vitro antimalarial activity against Plasmodium falciparum (P. falciparum), both chloroquine-sensitive (60 nM) and chloroquine-resistant (177 nM) parasites. FNDR-10132 was evaluated for its antimalarial activity in vivo against the chloroquine-resistant strain Plasmodium yoelii N67 in Swiss mice. The oral administration of 100 mg/kg of FNDR-10132 showed 44% parasite suppression on day 4, with a mean survival time of 13.5 ± 2.3 days vs. 8.4 ± 2.3 days of control. Also, FNDR-10132 displayed equivalent activity against the resistant strains of P. falciparum in the 200–300 nM range. This study offers a novel series of antimalarial compounds that could be developed into potent drugs against chloroquine-resistant malarial parasites through further chemistry and DMPK optimization.
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spelling pubmed-106102892023-10-28 Novel Baicalein-Derived Inhibitors of Plasmodium falciparum Gudla, Chandra Sekhar Selvam, Vignesh Selvaraj, Siva Shanmugam Tripathi, Renu Joshi, Prince Shaham, Salique Hassan Singh, Mayas Shandil, Radha Krishan Habib, Saman Narayanan, Shridhar Pathogens Article Malaria, a life-threatening mosquito-borne disease caused by Plasmodium parasites, continues to pose a significant global health burden. Despite notable progress in combating the disease in recent years, malaria remains prevalent in many regions, particularly in Southeast Asia and most of sub-Saharan Africa, where it claims hundreds of thousands of lives annually. Flavonoids, such as the baicalein class of compounds, are known to have antimalarial properties. In this study, we rationally designed and synthesized a series of baicalein derivatives and identified a lead compound, FNDR-10132, that displayed potent in vitro antimalarial activity against Plasmodium falciparum (P. falciparum), both chloroquine-sensitive (60 nM) and chloroquine-resistant (177 nM) parasites. FNDR-10132 was evaluated for its antimalarial activity in vivo against the chloroquine-resistant strain Plasmodium yoelii N67 in Swiss mice. The oral administration of 100 mg/kg of FNDR-10132 showed 44% parasite suppression on day 4, with a mean survival time of 13.5 ± 2.3 days vs. 8.4 ± 2.3 days of control. Also, FNDR-10132 displayed equivalent activity against the resistant strains of P. falciparum in the 200–300 nM range. This study offers a novel series of antimalarial compounds that could be developed into potent drugs against chloroquine-resistant malarial parasites through further chemistry and DMPK optimization. MDPI 2023-10-13 /pmc/articles/PMC10610289/ /pubmed/37887758 http://dx.doi.org/10.3390/pathogens12101242 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gudla, Chandra Sekhar
Selvam, Vignesh
Selvaraj, Siva Shanmugam
Tripathi, Renu
Joshi, Prince
Shaham, Salique Hassan
Singh, Mayas
Shandil, Radha Krishan
Habib, Saman
Narayanan, Shridhar
Novel Baicalein-Derived Inhibitors of Plasmodium falciparum
title Novel Baicalein-Derived Inhibitors of Plasmodium falciparum
title_full Novel Baicalein-Derived Inhibitors of Plasmodium falciparum
title_fullStr Novel Baicalein-Derived Inhibitors of Plasmodium falciparum
title_full_unstemmed Novel Baicalein-Derived Inhibitors of Plasmodium falciparum
title_short Novel Baicalein-Derived Inhibitors of Plasmodium falciparum
title_sort novel baicalein-derived inhibitors of plasmodium falciparum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610289/
https://www.ncbi.nlm.nih.gov/pubmed/37887758
http://dx.doi.org/10.3390/pathogens12101242
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