Plasmodium falciparum PFI1625c offers an opportunity to design potent anti-malarials: Biochemical characterization and testing potentials in drug discovery

Lhouvum, Kimjolly; Balaji, Shruti; Ahsan, Mohamed Jawed; Trivedi, Vishal

doi:10.1016/j.actatropica.2018.12.033

“…6). However, presumably ABS parasites still have a comparably high need for MPP activity to facilitate mitochondrial function outside of respiration, as exemplified by putative MPPβ inhibitors showing promise as antimalarials 79,80 .…”

Section: Discussionmentioning

confidence: 99%

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

Evers

¹

,

Cabrera‐Orefice

²

,

Elurbe

³

et al. 2021

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Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and the transmissible gametocyte stages of Plasmodium falciparum. We identify remarkably divergent composition and clade-specific additions of all respiratory chain complexes. Furthermore, we show that respiratory chain complex components and linked metabolic pathways are up to 40-fold more prevalent in gametocytes, while glycolytic enzymes are substantially reduced. Underlining this functional switch, we find that cristae are exclusively present in gametocytes. Leveraging these divergent properties and stage dynamics for drug development presents an attractive opportunity to discover novel classes of antimalarials and increase our repertoire of gametocytocidal drugs.

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“…6). However, presumably ABS parasites still have a comparably high need for MPP activity to facilitate mitochondrial function outside of respiration, as exemplified by putative MPPβ inhibitors showing promise as antimalarials (77,78). This would necessitate synthesis of the whole complex, which is much less efficient and more challenging from a regulatory standpoint than generating the heterodimer observed in the mitochondria of its host.…”

Section: Discussionmentioning

confidence: 99%

Composition and stage dynamics of mitochondrial complexes inPlasmodium falciparum

Evers¹,

Cabrera‐Orefice

²

,

Elurbe

³

et al. 2020

Preprint

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Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and the transmissible gametocyte stages of Plasmodium falciparum. We identify remarkably divergent composition and clade-specific additions of all respiratory chain complexes. Furthermore, we show that respiratory chain complex components and linked metabolic pathways are up to 40-fold more prevalent in gametocytes, while glycolytic enzymes are substantially reduced. Underlining this functional switch, we find that cristae are exclusively present in gametocytes. Leveraging these divergent properties and stage dynamics for drug development presents an attractive opportunity to discover novel classes of antimalarials and increase our repertoire of gametocytocidal drugs.

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“…13 C NMR (100 MHz, CDCl 3 ), δ ppm: 20. 8,77.9,103.5,113.6,121.6,126.7,127.0,127.3,127.8,128.8,128.8,129.7,130.0,130.7,131.3,132.0,137.1,141.1. MS (EI,70 eV): m/z (%) = 336 (M + , 60), 335 (100), 334 (19), 245 (13), 217 (13), 207 (12), 194 (18), 91 (28), 77 (16), 65 (21).…”

Section: Papermentioning

confidence: 99%

“…3 Among them there are certain distinctive substances containing the 2-arylvinyl (styryl) group at various positions of a heterocycle, as well as their analogs. 4 Styrylpyrazoles, styrylpyrazolines and similarly structured substances possess antitumor, 5 antioxidative, 5 l,o ,6 antibacterial, 7 antimalarial, 8 antifungal, 9 and anti-inflammatory 10 properties, and some other types of biological activities 11 (also see the references in the review by Gomes and coworkers 4 for details). Furthermore, styrylpyrazoles have valuable photophysical abilities.…”

Section: Introductionmentioning

confidence: 99%

Cyclization of arylhydrazones of cross-conjugated enynones: synthesis of luminescent styryl-1H-pyrazoles and propenyl-1H-pyrazoles

Itakhunov

¹

,

Odin

²

,

Gusev

³

et al. 2022

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Plasmodium falciparum PFI1625c offers an opportunity to design potent anti-malarials: Biochemical characterization and testing potentials in drug discovery

Cited by 7 publications

References 63 publications

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

Composition and stage dynamics of mitochondrial complexes inPlasmodium falciparum

Cyclization of arylhydrazones of cross-conjugated enynones: synthesis of luminescent styryl-1H-pyrazoles and propenyl-1H-pyrazoles

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