Delving into the Latest Updates on Tribendimidine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

力卓

Target-

Mechanism-

Therapeutic Areas

Infectious Diseases

Active Indication

AscariasisHookworm Infections

Inactive Indication-

Originator Organization

Shandong Xinhua Pharmaceutical Co., Ltd.

Active Organization

Shandong Xinhua Pharmaceutical Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (30 Apr 2004),

AscariasisHookworm Infections

Regulation-

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Structure

Molecular FormulaC28H32N6

InChIKeyXOIOGKHKNQYULW-UHFFFAOYSA-N

CAS Registry115103-15-6

Trichuriasis is a neglected tropical disease widely distributed among tropical and sub-tropical areas and associated with poverty and lack of access to safe drinking water, sanitation and hygiene. Existing drugs have limited efficacy and face a constant risk of developing resistance, necessitating the search for alternative treatments. However, drug discovery efforts are sparse and little research has been performed on anthelminthic effects on embryonated eggs, the infectious life stage of Trichuris spp. We examined bacterial species dependent egg hatching of the murine model parasite Trichuris muris and identified Escherichia coli, Pseudomonas aeruginosa and Enterobacter hormaechei effective as hatching inducers, resulting in hatching yields of 50-70%. Streptococcus salivarius, reported to be associated with reduced drug efficacy of ivermectin-albendazole coadministration in Trichuris trichiura infected patients, did not promote egg hatching in vitro. We optimized hatching conditions using E. coli grown in luria broth or brain-heart infusion media to reach consistently high hatching yields to provide a sensitive, robust and simple egg-hatching assay. Oxantel pamoate demonstrated the strongest potency in preventing hatching, with an EC₅₀ value of 2-4 μM after 24 h, while pyrantel pamoate, levamisole and tribendimidine exhibited only moderate to weak inhibitory effects. Conversely, all tested benzimidazoles and macrolide anthelminthics as well as emodepside failed to prevent hatching (EC₅₀ > 100 μM). Our study demonstrates that egg-hatching assays complement larval and adult stage drug sensitivity assays, to expand knowledge about effects of current anthelminthics on Trichuris spp. Further, the developed T. muris egg-hatching assay provides a simple and cheap screening tool that could potentially lead to the discovery of novel anthelminthic compounds.

04 May 2023·Parasites & vectors

Development of a hookworm egg hatching assay to determine the ovicidal effects of anthelminthics

Article

Author: Easland, Erin ; Keiser, Jennifer ; Biendl, Stefan

Few anthelminthics are currently available, manifesting the urgent need for new treatment options.In vitro profiling of current anthelminthics against larval and adult stage helminths displayed varying effects on closely related worm species and between life stages of the same species.Conversely, limited research has been performed on the egg stage of human hookworms, and the effects of investigational compounds on the egg stage are not routinely assessed.We profiled the development and hatching of Heligmosomoides polygyrus, Ancylostoma duodenale and Necator americanus eggs isolated from rodent faeces in liquid media with various nutrient levels, osmolar concentrations, and acidities in dependence on incubation temperature and light exposure.Incubation conditions were optimized to allow the study of drug effect on immature and embryonated eggs.We analyzed concentration-effect relationships of com. available anthelminthics over 72 h.Rapid embryonation and hatching were observed at room temperature with and without light exposure without nutrient supplementation in a wide range of acidities.Hookworms hatched optimally at room temperature in PBS achieving > 75% hatching over 34 h.Developmental delays were seen when eggs were stored at 4°C with no effect on viability.Similar delays were also seen with increased osmolar concentrations resulting in decreased viability.Benzimidazole anthelminthics effectively reduced the viability and prevented hatching of hookworm eggs, with albendazole and thiabendazole eliciting particularly potent effects at EC50 values below 1μM.Macrolide anthelminthics as well as emodepside, oxantel pamoate, and pyrantel pamoate were inactive while monepantel, levamisole, and tribendimidine displayed varied potencies among the hookworm species.The presented egg-hatching assay will complement ongoing anthelminthic drug discovery and allow a full characterization of drug activity against all life stages.In the development and application of the egg-hatching assay, good accordance was observed between the three hookworm species evaluated.Marketed anthelminthics show differences of drug action compared to larval and adult stages highlighting the importance of profiling drug activity against all life stages.

01 Jun 2022·Acta TropicaQ3 · MEDICINE

Metabolome alterations in Clonorchis sinensis after treatment with tribendimidine and praziquante in vivo

Q3 · MEDICINE

Article

Author: Mingyong, Liang ; Xinru, Liu ; Jian, Xue ; Yufen, Wei ; Huolele ; Yu, Chen ; Zhihua, Jiang ; Haobing, Zhang

Tribendimidine (TBD) is a broad-spectrum anthelmintic drug that is also significantly effective in treating clonorchiasis. In this study, the altered metabolomes of Clonorchis sinensis (C. sinensis) in rats after TBD administration were quantified by using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) to explore the possible active sites of TBD against clonorchiasis through altered metabolites and metabolic pathway analysis, and the results are expected to provide a target for the future design of anti-Clonorchis sinensis drugs. The worm burden reduction rate and scanning electron microscopy demonstrated that praziquantel (PZQ, positive control drug) and TBD had significant effects on C. sinensis in rats after treatment at a single dose of 200 mg/kg for 24 h. For the MS-based metabolomic analysis, a total of 173 standard metabolites (126 amino acids, 10 phospholipids and 37 fatty acids) were utilized as a reference metabolite database for metabolome identification. In total, 32 amino acids, 71 phospholipids and 27 fatty acids were detected in the C. sinensis of each group. Among these metabolites, 10 amino acids were significantly decreased in both drug-treated groups. Four lysophosphatidyl cholines (LPCs), six lysophosphatidyl ethanolamines (LPEs) and one phosphatidyl inositol (PI) were significantly increased after treatment with TBD. There were no significant changes in fatty acids among the control group and the two drug-treated groups. The results indicated that TBD administration caused a decrease in amino acids involved in the metabolic pathways of energy consumption and an increase in lysophospholipids, which are the hydrolysis products of phospholipase2 (PLA2) in the phospholipid metabolic pathways. The increased lysophospholipid content can destroy the cell membrane, increase membrane permeability, and even cause exposure to internal antigens that can be attacked by host antibodies. Perhaps the destroyed membrane, the exposed internal antigens and the consumed energy are the cause of the damage and death of C. sinensis after TBD administration. This is an interesting problem that can be examined in future research.

100 Deals associated with Tribendimidine

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Ascariasis	CN	Shandong Xinhua Pharmaceutical Co., Ltd.	30 Apr 2004
Hookworm Infections	CN	Shandong Xinhua Pharmaceutical Co., Ltd.	30 Apr 2004

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ISRCTN81391471 (Pubmed \| Clin Infect Dis)	Phase 2	Hookworm Infections	130	Placebo	(gajqbmxczy) = melofiifra zolcqzmite (dywwnabbdv ) View more	-	16 Aug 2019
				100 mg tribendimidine	(gajqbmxczy) = llhkcaevbh zolcqzmite (dywwnabbdv ) View more
ISRCTN96948551 (Pubmed \| Antimicrob Agents Chemother)	Not Applicable	Opisthorchiasis	68	25-mg dose of tribendimidine using 50-mg tablet formulation	(dofpvfjhpa) = uuufgwzueh zvvmowciek (oxbuhujiyf )	-	01 Oct 2016
				600-mg dose of tribendimidine using 200-mg tablet formulation	(dofpvfjhpa) = nvcukxsjpg zvvmowciek (oxbuhujiyf )
ISRCTN55086560 (Pubmed)	Not Applicable	Clonorchiasis	156	Single-dose tribendimidine 400 mg	fxjdsaawos(iikolnwwod) = Adverse events caused by tribendimidine were significantly less than praziquantel lohgazwchw (fkhpgggdjv )	-	01 Aug 2014
				75 mg/kg praziquantel
ISRCTN80829842 (Controlled-Trials.com, Pubmed)	Not Applicable	Clonorchiasis	74	400 mg tribendimidine once	(ykzmxfvfci) = Patients treated with praziquantel experienced significantly more adverse events than did tribendimidine recipients (P < .05) jrejdosodx (ylzyfspogi )	-	01 Apr 2013
				400 mg tribendimidine daily for 3 days
ISRCTN23425032 (Pubmed \| Lancet Infect Dis)	Phase 2	Opisthorchiasis	125	Artesunate	rlelhjgrkw(vbvjyarxwv) = wrvyuislmh rnrfdkvdiw (pqywibsmln )	-	01 Feb 2011
				Mefloquine-artesunate	rlelhjgrkw(vbvjyarxwv) = fvgrobvdaf rnrfdkvdiw (pqywibsmln )