Gossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolates

Abstract Gossypol has demonstrated significant antimalarial activity against chloroquine-resistant and susceptible Plasmodium falciparum parasites. However, data on its potency in clinical isolates of P. falciparum remains limited. This study aimed to assess the potency of gossypol against six labor...

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Main Authors: Jersley D. Chirawurah, Felix Ansah, Samuel Blankson, Bridget Adikah, Silas Nkansah Yeboah, Lucas Amenga-Etego, Gordon A. Awandare, Yaw Aniweh
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-85643-6
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author Jersley D. Chirawurah
Felix Ansah
Samuel Blankson
Bridget Adikah
Silas Nkansah Yeboah
Lucas Amenga-Etego
Gordon A. Awandare
Yaw Aniweh
author_facet Jersley D. Chirawurah
Felix Ansah
Samuel Blankson
Bridget Adikah
Silas Nkansah Yeboah
Lucas Amenga-Etego
Gordon A. Awandare
Yaw Aniweh
author_sort Jersley D. Chirawurah
collection DOAJ
description Abstract Gossypol has demonstrated significant antimalarial activity against chloroquine-resistant and susceptible Plasmodium falciparum parasites. However, data on its potency in clinical isolates of P. falciparum remains limited. This study aimed to assess the potency of gossypol against six laboratory strains and twenty-one clinical isolates of P. falciparum using optimized growth inhibition assays. Additionally, parasites with reduced susceptibility to gossypol were selected using the P. falciparum Dd2 background (Dd2_3.5 µM) and tested for cross-resistance to chloroquine, dihydroartemisinin (DHA), and three Malaria box compounds (MMV006087, MMV085203, and MMV008956). On average, gossypol was found to be twice as potent against the laboratory strains compared to the clinical isolates, with IC₅₀ values of 6.490 µM and 11.670 µM, respectively. Notably, Dd2_3.5 µM parasites displayed increased sensitivity after three months of exposure but developed decreased susceptibility after six months. Importantly, these gossypol-tolerant parasites showed no cross-resistance to chloroquine, DHA, or the three Malaria box compounds. These findings suggest that gossypol is effective against P. falciparum and holds potential as part of combination therapy with existing antimalarials. Furthermore, these results may support the identification of new antimalarial agents that are effective against drug-resistant malaria parasites.
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spelling doaj-art-fa5a1a6324664751ab82b9ec786c28b12025-01-12T12:19:55ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-025-85643-6Gossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolatesJersley D. Chirawurah0Felix Ansah1Samuel Blankson2Bridget Adikah3Silas Nkansah Yeboah4Lucas Amenga-Etego5Gordon A. Awandare6Yaw Aniweh7West African Centre for Cell Biology of Infectious Pathogens, University of GhanaWest African Centre for Cell Biology of Infectious Pathogens, University of GhanaWest African Centre for Cell Biology of Infectious Pathogens, University of GhanaWest African Centre for Cell Biology of Infectious Pathogens, University of GhanaWest African Centre for Cell Biology of Infectious Pathogens, University of GhanaWest African Centre for Cell Biology of Infectious Pathogens, University of GhanaWest African Centre for Cell Biology of Infectious Pathogens, University of GhanaWest African Centre for Cell Biology of Infectious Pathogens, University of GhanaAbstract Gossypol has demonstrated significant antimalarial activity against chloroquine-resistant and susceptible Plasmodium falciparum parasites. However, data on its potency in clinical isolates of P. falciparum remains limited. This study aimed to assess the potency of gossypol against six laboratory strains and twenty-one clinical isolates of P. falciparum using optimized growth inhibition assays. Additionally, parasites with reduced susceptibility to gossypol were selected using the P. falciparum Dd2 background (Dd2_3.5 µM) and tested for cross-resistance to chloroquine, dihydroartemisinin (DHA), and three Malaria box compounds (MMV006087, MMV085203, and MMV008956). On average, gossypol was found to be twice as potent against the laboratory strains compared to the clinical isolates, with IC₅₀ values of 6.490 µM and 11.670 µM, respectively. Notably, Dd2_3.5 µM parasites displayed increased sensitivity after three months of exposure but developed decreased susceptibility after six months. Importantly, these gossypol-tolerant parasites showed no cross-resistance to chloroquine, DHA, or the three Malaria box compounds. These findings suggest that gossypol is effective against P. falciparum and holds potential as part of combination therapy with existing antimalarials. Furthermore, these results may support the identification of new antimalarial agents that are effective against drug-resistant malaria parasites.https://doi.org/10.1038/s41598-025-85643-6
spellingShingle Jersley D. Chirawurah
Felix Ansah
Samuel Blankson
Bridget Adikah
Silas Nkansah Yeboah
Lucas Amenga-Etego
Gordon A. Awandare
Yaw Aniweh
Gossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolates
Scientific Reports
title Gossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolates
title_full Gossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolates
title_fullStr Gossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolates
title_full_unstemmed Gossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolates
title_short Gossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolates
title_sort gossypol is a natural product with good antimalarial activity against plasmodium falciparum clinical isolates
url https://doi.org/10.1038/s41598-025-85643-6
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