Structure-activity profiling of alkaloid natural product pharmacophores against a Schistosoma serotonin receptor

Marchant, Jonathan S.; Harding, Wayne W.; Chan, John D.

doi:10.1016/j.ijpddr.2018.09.001

Cited by 11 publications

(5 citation statements)

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“…Schistosomes express a broad GPCR portfolio [65], and the predicted serotoninergic GPCRs are of high interest given the role of this neurotransmitter in parasite movement [62]. From the complement of predicted 5-HT GPCRs, only the pharmacological profile of a single schistosome 5-HTR (Sm.7a L [44,56,66], and orthologs Sj.7a, Sh.7a [56]) have been well studied to date, enabled by successful heterologous expression in mammalian cell lines. In vivo RNAi of Sm.7a [62] or a planarian homolog [39], and application of 5-HT ligands validated at these targets, all disrupted worm movement [39,43,44,56,67].…”

Section: Pzq Targets: Definitive In the Hostmentioning

confidence: 99%

The Journey to Discovering a Flatworm Target of Praziquantel: A Long TRP

Park

Marchant

2020

Trends in Parasitology

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Infections caused by parasitic flatworms impose a considerable worldwide health burden. One of the most impactful is schistosomiasis, a disease caused by parasitic blood flukes. Treatment of schistosomiasis has relied on a single drug -praziquantel (PZQ) -for decades. The utility of PZQ as an essential medication is, however, intertwined with a stark gap in our knowledge as to how this drug works. No flatworm target has been identified that readily explains how PZQ paralyzes and damages schistosomes. Recently, a schistosome ion channel was discovered that is activated by PZQ and displays characteristics which mirror key features of PZQ action on schistosomes. Here, the journey to discovery of this target, properties of this ion channel, and remaining questions are reviewed.

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Section: Pzq Targets: Definitive In the Hostmentioning

confidence: 99%

The Journey to Discovering a Flatworm Target of Praziquantel: A Long TRP

Park

Marchant

2020

Trends in Parasitology

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“…Three receptors also resembled Sm5HTR in phylogenetic analysis, being likely 5-HT receptors [113]. Thus, the 5-HT 7 receptors have been described in the members of the Platyhelminthes phylum and this receptor type appears to be the dominant clade in this group of organisms [60,82,105,110,113,114].…”

Section: Discussionmentioning

confidence: 76%

Serotonin Signalling in Flatworms: An Immunocytochemical Localisation of 5-HT7 Type of Serotonin Receptors in Opisthorchis felineus and Hymenolepis diminuta

2021

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The study is dedicated to the investigation of serotonin (5-hydroxytryptamine, 5-HT) and 5-HT7 type serotonin receptor of localisation in larvae of two parasitic flatworms Opisthorchis felineus (Rivolta, 1884) Blanchard, 1895 and Hymenolepis diminuta Rudolphi, 1819, performed using the immunocytochemical method and confocal laser scanning microscopy (CLSM). Using whole mount preparations and specific antibodies, a microscopic analysis of the spatial distribution of 5-HT7-immunoreactivity(-IR) was revealed in worm tissue. In metacercariae of O. felineus 5-HT7-IR was observed in the main nerve cords and in the head commissure connecting the head ganglia. The presence of 5-HT7-IR was also found in several structures located on the oral sucker. 5-HT7-IR was evident in the round glandular cells scattered throughout the larva body. In cysticercoids of H. diminuta immunostaining to 5-НТ7 was found in flame cells of the excretory system. Weak staining to 5-HT7 was observed along the longitudinal and transverse muscle fibres comprising the body wall and musculature of suckers, in thin longitudinal nerve cords and a connective commissure of the central nervous system. Available publications on serotonin action in flatworms and serotonin receptors identification were reviewed. Own results and the published data indicate that the muscular structures of flatworms are deeply supplied by 5-HT7-IR elements. It suggests that the 5-HT7 type receptor can mediate the serotonin action in the investigated species and is an important component of the flatworm motor control system. The study of the neurochemical basis of parasitic flatworms can play an important role in the solution of fundamental problems in early development of the nervous system and the evolution of neuronal signalling components.

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“…The parasitic blood fluke, Schistosoma mansoni , produces serotonin (5-HT) which targets the cyclic Adenosine Monophosphate (cAMP) to regulate the parasite movement. Marchant et al proposed a co-expressed Sm.5HTRL receptor in mammalian cells beside a luminescent cAMP-biosensor for finding the anti-schistosomal drug candidates such as aporphines, protoberberines, and tryptamines which was previously shown to regulate Sm.5HTRL [ 118 ].…”

Section: Emerging Biosensor-based Detection Methods Of Natural Producmentioning

confidence: 99%

Emerging biosensors in detection of natural products

Piroozmand

Mohammadipanah

Faridbod

2020

Synthetic and Systems Biotechnology

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Natural products (NPs) are a valuable source in the food, pharmaceutical, agricultural, environmental, and many other industrial sectors. Their beneficial properties along with their potential toxicities make the detection, determination or quantification of NPs essential for their application. The advanced instrumental methods require time-consuming sample preparation and analysis. In contrast, biosensors allow rapid detection of NPs, especially in complex media, and are the preferred choice of detection when speed and high throughput are intended. Here, we review diverse biosensors reported for the detection of NPs. The emerging approaches for improving the efficiency of biosensors, such as microfluidics, nanotechnology, and magnetic beads, are also discussed. The simultaneous use of two detection techniques is suggested as a robust strategy for precise detection of a specific NP with structural complexity in complicated matrices. The parallel detection of a variety of NPs structures or biological activities in a mixture of extract in a single detection phase is among the anticipated future advancements in this field which can be achieved using multisystem biosensors applying multiple flow cells, sensing elements, and detection mechanisms on miniaturized folded chips.

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Structure-activity profiling of alkaloid natural product pharmacophores against a Schistosoma serotonin receptor

Cited by 11 publications

References 50 publications

The Journey to Discovering a Flatworm Target of Praziquantel: A Long TRP

The Journey to Discovering a Flatworm Target of Praziquantel: A Long TRP

Serotonin Signalling in Flatworms: An Immunocytochemical Localisation of 5-HT7 Type of Serotonin Receptors in Opisthorchis felineus and Hymenolepis diminuta

Emerging biosensors in detection of natural products

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