Synergistic interaction of two antimalarial drugs, artemisinin and concanamycin A

Artemisinin is a powerful drug that has been combined with other antimalarial drugs to combat malaria and it has been crucial to recent achievements in reducing malaria cases. However, the emergence of Plasmodium falciparum resistance against artemisinin has become a serious problem in malaria treat...

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Main Authors: Nurul Izzaty Najwa Zahari, Noor Fardziatun Ujal, Nurhidanatasha Abu-Bakar
Format: Article
Language:English
Published: Biome Scientia 2023-06-01
Series:Life Sciences, Medicine and Biomedicine
Subjects:
Online Access:https://biomescientia.com/index.php/lsmb/article/view/107
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author Nurul Izzaty Najwa Zahari
Noor Fardziatun Ujal
Nurhidanatasha Abu-Bakar
author_facet Nurul Izzaty Najwa Zahari
Noor Fardziatun Ujal
Nurhidanatasha Abu-Bakar
author_sort Nurul Izzaty Najwa Zahari
collection DOAJ
description Artemisinin is a powerful drug that has been combined with other antimalarial drugs to combat malaria and it has been crucial to recent achievements in reducing malaria cases. However, the emergence of Plasmodium falciparum resistance against artemisinin has become a serious problem in malaria treatment. Our previous studies reported that artemisinin alkalinised the digestive vacuole of P. falciparum similarly to concanamycin A. Concanamycin A is a specific inhibitor of V-type H+-ATPase, a proton pump located on the membrane of the digestive vacuole. A study also showed that a low concentration of concanamycin A is required to kill 50% of the parasites. Therefore, this study aimed to determine the interaction of artemisinin with concanamycin A by using the isobologram analysis of effects on parasite growth. The antimalarial activity (IC50) of artemisinin and concanamycin A was evaluated by using a malarial SBYR Green I fluorescence-based (MSF) assay prior to isobologram analysis. Based on their IC50 values, six different combination solutions of the drugs were assigned and used in the isobologram analysis. The IC50 of artemisinin and concanamycin A was 13 ± 2.52 nM and 7 ± 1.15 nM, respectively. The interaction of artemisinin and concanamycin A was found to be synergistic, indicating that the combination of these drugs could kill the parasites more effectively. This study suggests that artemisinin and concanamycin A combination can be a new candidate in artemisinin-based combination therapies.
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spelling doaj.art-47973199834b4b39899e1040050324712023-06-16T04:07:01ZengBiome ScientiaLife Sciences, Medicine and Biomedicine2600-72072023-06-017110.28916/lsmb.7.1.2023.10785Synergistic interaction of two antimalarial drugs, artemisinin and concanamycin ANurul Izzaty Najwa Zahari0Noor Fardziatun Ujal1Nurhidanatasha Abu-Bakar2School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.Artemisinin is a powerful drug that has been combined with other antimalarial drugs to combat malaria and it has been crucial to recent achievements in reducing malaria cases. However, the emergence of Plasmodium falciparum resistance against artemisinin has become a serious problem in malaria treatment. Our previous studies reported that artemisinin alkalinised the digestive vacuole of P. falciparum similarly to concanamycin A. Concanamycin A is a specific inhibitor of V-type H+-ATPase, a proton pump located on the membrane of the digestive vacuole. A study also showed that a low concentration of concanamycin A is required to kill 50% of the parasites. Therefore, this study aimed to determine the interaction of artemisinin with concanamycin A by using the isobologram analysis of effects on parasite growth. The antimalarial activity (IC50) of artemisinin and concanamycin A was evaluated by using a malarial SBYR Green I fluorescence-based (MSF) assay prior to isobologram analysis. Based on their IC50 values, six different combination solutions of the drugs were assigned and used in the isobologram analysis. The IC50 of artemisinin and concanamycin A was 13 ± 2.52 nM and 7 ± 1.15 nM, respectively. The interaction of artemisinin and concanamycin A was found to be synergistic, indicating that the combination of these drugs could kill the parasites more effectively. This study suggests that artemisinin and concanamycin A combination can be a new candidate in artemisinin-based combination therapies.https://biomescientia.com/index.php/lsmb/article/view/107artemisininconcanamycin aplasmodium falciparumproton pumpisobologram analysis
spellingShingle Nurul Izzaty Najwa Zahari
Noor Fardziatun Ujal
Nurhidanatasha Abu-Bakar
Synergistic interaction of two antimalarial drugs, artemisinin and concanamycin A
Life Sciences, Medicine and Biomedicine
artemisinin
concanamycin a
plasmodium falciparum
proton pump
isobologram analysis
title Synergistic interaction of two antimalarial drugs, artemisinin and concanamycin A
title_full Synergistic interaction of two antimalarial drugs, artemisinin and concanamycin A
title_fullStr Synergistic interaction of two antimalarial drugs, artemisinin and concanamycin A
title_full_unstemmed Synergistic interaction of two antimalarial drugs, artemisinin and concanamycin A
title_short Synergistic interaction of two antimalarial drugs, artemisinin and concanamycin A
title_sort synergistic interaction of two antimalarial drugs artemisinin and concanamycin a
topic artemisinin
concanamycin a
plasmodium falciparum
proton pump
isobologram analysis
url https://biomescientia.com/index.php/lsmb/article/view/107
work_keys_str_mv AT nurulizzatynajwazahari synergisticinteractionoftwoantimalarialdrugsartemisininandconcanamycina
AT noorfardziatunujal synergisticinteractionoftwoantimalarialdrugsartemisininandconcanamycina
AT nurhidanatashaabubakar synergisticinteractionoftwoantimalarialdrugsartemisininandconcanamycina