Docosahexaenoic acid is potent against the growth of mature stages of Plasmodium falciparum; inhibition of hematin polymerization a possible target

Ommi, Naidu Babu; Abdullah, Maaged; Guruprasad, Lalitha; Babu, Phanithi Prakash

doi:10.1016/j.parint.2022.102581

Cited by 2 publications

References 43 publications

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In silico analysis of the action of saturated, monounsaturated, and polyunsaturated fatty acids against Echinococcus granulosus fatty-acid-binding protein 1

Paco-Chipana,

Mena-Ulecia,

Hidalgo Rosa

et al. 2024

F1000Res

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Background The zoonotic infection caused by tapeworms Echinococcus is a neglected tropical disease in poor regions with limited access to suitable sanitary conditions. Hydatid cysts produced by Echinococcus granulosus use fatty-acid-binding proteins (FABP) to obtain the fatty acids and cholesterol necessary for their survival from the host. In this work, we analyzed the behaviour of saturated, monounsaturated, and polyunsaturated fatty acids against EgFABP1. Methods We used computational biology and chemistry techniques and binding free energy estimations by molecular mechanics generalized Born surface area (MM/GBSA). Results This research has enabled us to clarify the EgFABP1 isoforms identified in the database, suggesting their potential involvement in diverse cellular activities of Echinococcus granulosus. Conversely, examining the global and local chemical reactivity of 14 fatty acids revealed that liposolubility is contingent upon the degree of unsaturation in the FAs. Additionally, FAs exhibited acceptable levels of oral absorption and bioavailability. The binding of EgFABP1 with FAs analyzed by molecular dynamics simulation showed us that these are highly stable, where the best affinity was with docosahexaenoic acid. Conclusions Our results suggest that the action of fatty acids could play an interesting role in detecting early Echinococcus granulosus.

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In silico analysis of the action of saturated, monounsaturated, and polyunsaturated fatty acids against Echinococcus granulosus fatty-acid-binding protein 1

Paco-Chipana,

Mena-Ulecia,

Hidalgo Rosa

et al. 2024

F1000Res

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Hemozoin: a waste product after heme detoxification?

Sun,

Qin,

et al. 2024

Preprint

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Hemozoin is consider a waste byproduct of heme detoxification following hemoglobin digestion; consequently, the biological functions of hemozoin in hemozoin-producing organisms have often been overlooked. However, recent findings indicate that schistosoma hemozoin facilitates the transfer of iron from erythrocytes to eggs through its formation and degradation, thereby increasing interest in the role of malarial hemozoin. In this study, we compared the formation of schistosoma hemozoin and malaria hemozoin using transmission electron microscopy, which suggests why the trophozoite stage cannot eliminate hemozoin. Additionally, through transcriptome analysis of different stages of P. falciparum 3D7WT and P. falciparum 3D7C580Y- where the latter serves as a control with lower hemozoin production-we found that both exhibit similar expression patterns in genes related to DNA synthesis, iron, and heme utilization. Notably, during the trophozoite stage, expression levels of these genes in P. falciparum 3D7WT are higher than in P. falciparum 3D7C580Y, whereas during the schizont stage, they are lower. These results suggest that when P. falciparum 3D7 utilizes more heme and iron, it produces less hemozoin, whereas when it utilizes less heme and iron, it produces more hemozoin. Interrupting heme utilization and destructing hemozoin aggregation can result in parasite death. Additionally, the hemozoin released by schizonts can impair macrophage functions, or it is carried by gametocytes into the next host without being discharged as waste, suggesting that the release of malaria hemozoin protects merozoites from phagocytosis, and its transfer to the next host may fulfill the requirements for iron and heme during their development in mosquitoes.

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Docosahexaenoic acid is potent against the growth of mature stages of Plasmodium falciparum; inhibition of hematin polymerization a possible target

Cited by 2 publications

References 43 publications

In silico analysis of the action of saturated, monounsaturated, and polyunsaturated fatty acids against Echinococcus granulosus fatty-acid-binding protein 1

In silico analysis of the action of saturated, monounsaturated, and polyunsaturated fatty acids against Echinococcus granulosus fatty-acid-binding protein 1

Hemozoin: a waste product after heme detoxification?

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