MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasites
The emergence of drug-resistant malaria parasites to artemisinin and its partner drugs highlights the need to increase the arsenal of new antimalarials with novel mechanisms of action. To help achieve this aim, this study tested the potency of three Malaria Box compounds (MMV006087, MMV085203, and M...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Drug Discovery |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fddsv.2023.1190471/full |
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| author | Jersley D. Chirawurah Jersley D. Chirawurah Bridget Adikah Bridget Adikah Felix Ansah Felix Ansah Elizabeth Laryea-Akrong Elizabeth Laryea-Akrong Harry Danwonno Harry Danwonno Collins M. Morang’a Collins M. Morang’a Daniel Dosoo Daniel Dosoo Lucas Amenga-Etego Lucas Amenga-Etego Gordon A. Awandare Gordon A. Awandare Yaw Aniweh Yaw Aniweh |
| author_facet | Jersley D. Chirawurah Jersley D. Chirawurah Bridget Adikah Bridget Adikah Felix Ansah Felix Ansah Elizabeth Laryea-Akrong Elizabeth Laryea-Akrong Harry Danwonno Harry Danwonno Collins M. Morang’a Collins M. Morang’a Daniel Dosoo Daniel Dosoo Lucas Amenga-Etego Lucas Amenga-Etego Gordon A. Awandare Gordon A. Awandare Yaw Aniweh Yaw Aniweh |
| author_sort | Jersley D. Chirawurah |
| collection | DOAJ |
| description | The emergence of drug-resistant malaria parasites to artemisinin and its partner drugs highlights the need to increase the arsenal of new antimalarials with novel mechanisms of action. To help achieve this aim, this study tested the potency of three Malaria Box compounds (MMV006087, MMV085203, and MMV008956) against five laboratory strains and twenty clinical isolates of Plasmodium falciparum using optimized in vitro growth inhibitory assays. The results were compared to the response from four standard antimalarials-artesunate, chloroquine, mefloquine, and halofantrine. From the results, MMV006087 was the most potent compound with an average IC50 of 22.13 nM compared to MMV085203 (average IC50 of 137.90 nM) and MMV008956 (average IC50 of 262.30 nM). On average, the laboratory strains were also less susceptible to the three Malaria Box compounds (average IC50 of 162.30 nM) compared to the clinical isolates (average IC50 of 135.40 nM). Additionally, MMV006087 was less potent than artesunate but twice more efficacious than chloroquine against the laboratory strains and clinical isolates. The data from this study validate the potency of MMV006087 and MMV085203 as promising antimalarials worthy of further exploration. This study further substantiates the need to include clinical isolates in antimalarial compound screening activities. |
| first_indexed | 2024-03-13T05:26:32Z |
| format | Article |
| id | doaj.art-7d3373ab1347448e8b99bbbc57b5cc4d |
| institution | Directory Open Access Journal |
| issn | 2674-0338 |
| language | English |
| last_indexed | 2024-03-13T05:26:32Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Drug Discovery |
| spelling | doaj.art-7d3373ab1347448e8b99bbbc57b5cc4d2023-06-15T05:52:05ZengFrontiers Media S.A.Frontiers in Drug Discovery2674-03382023-06-01310.3389/fddsv.2023.11904711190471MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasitesJersley D. Chirawurah0Jersley D. Chirawurah1Bridget Adikah2Bridget Adikah3Felix Ansah4Felix Ansah5Elizabeth Laryea-Akrong6Elizabeth Laryea-Akrong7Harry Danwonno8Harry Danwonno9Collins M. Morang’a10Collins M. Morang’a11Daniel Dosoo12Daniel Dosoo13Lucas Amenga-Etego14Lucas Amenga-Etego15Gordon A. Awandare16Gordon A. Awandare17Yaw Aniweh18Yaw Aniweh19West African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, GhanaDepartment of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, GhanaDepartment of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, GhanaDepartment of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, GhanaDepartment of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, GhanaDepartment of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, GhanaDepartment of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, GhanaDepartment of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, GhanaDepartment of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, GhanaDepartment of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaWest African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, GhanaDepartment of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaThe emergence of drug-resistant malaria parasites to artemisinin and its partner drugs highlights the need to increase the arsenal of new antimalarials with novel mechanisms of action. To help achieve this aim, this study tested the potency of three Malaria Box compounds (MMV006087, MMV085203, and MMV008956) against five laboratory strains and twenty clinical isolates of Plasmodium falciparum using optimized in vitro growth inhibitory assays. The results were compared to the response from four standard antimalarials-artesunate, chloroquine, mefloquine, and halofantrine. From the results, MMV006087 was the most potent compound with an average IC50 of 22.13 nM compared to MMV085203 (average IC50 of 137.90 nM) and MMV008956 (average IC50 of 262.30 nM). On average, the laboratory strains were also less susceptible to the three Malaria Box compounds (average IC50 of 162.30 nM) compared to the clinical isolates (average IC50 of 135.40 nM). Additionally, MMV006087 was less potent than artesunate but twice more efficacious than chloroquine against the laboratory strains and clinical isolates. The data from this study validate the potency of MMV006087 and MMV085203 as promising antimalarials worthy of further exploration. This study further substantiates the need to include clinical isolates in antimalarial compound screening activities.https://www.frontiersin.org/articles/10.3389/fddsv.2023.1190471/fullantimalarialsmalariaclinical isolatesmalaria box compoundsartemisininmedicines for malaria venture |
| spellingShingle | Jersley D. Chirawurah Jersley D. Chirawurah Bridget Adikah Bridget Adikah Felix Ansah Felix Ansah Elizabeth Laryea-Akrong Elizabeth Laryea-Akrong Harry Danwonno Harry Danwonno Collins M. Morang’a Collins M. Morang’a Daniel Dosoo Daniel Dosoo Lucas Amenga-Etego Lucas Amenga-Etego Gordon A. Awandare Gordon A. Awandare Yaw Aniweh Yaw Aniweh MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasites Frontiers in Drug Discovery antimalarials malaria clinical isolates malaria box compounds artemisinin medicines for malaria venture |
| title | MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasites |
| title_full | MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasites |
| title_fullStr | MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasites |
| title_full_unstemmed | MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasites |
| title_short | MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasites |
| title_sort | mmv006087 is a potent malaria box compound against plasmodium falciparum clinical parasites |
| topic | antimalarials malaria clinical isolates malaria box compounds artemisinin medicines for malaria venture |
| url | https://www.frontiersin.org/articles/10.3389/fddsv.2023.1190471/full |
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