Antigiardial Activity of Novel Guanidine Compounds

Stevens, Andrew; Abraham, Rebecca; Young, Kelly A.; Russell, Cecilia C.; McCluskey, Siobhann N.; Baker, Jennifer R.; Rusdi, Bertha; Page, Stephen W.; O’Handley, Ryan; O’Dea, Mark; Abraham, Sam; McCluskey, Adam

doi:10.1002/cmdc.202200341

Cited by 5 publications

(2 citation statements)

References 42 publications

(107 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Robenidine, an anticoccidial drug classified as a guanidine derivative, showed better and faster activity than metronidazole against G. intestinalis with minimum lethal concentration (MLC) as low as 2.8 μM. Several analogs of this drug are developed, researched, and patented [51]. Azidothymidine (AZT), an anti-retroviral drug, also exhibits inhibitory activity in-vivo against Giardia, even against the metronidazole-resistant strains [52].…”

Section: Recent Drug Discovery Efforts Against Giardiasismentioning

confidence: 99%

Perspectives on the drug discovery of intestinal protozoan parasites

Thakur,

Sharma,

Negi

et al. 2024

Intestinal Parasites - New Developments in Diagnosis, Treatment, Prevention and Future Directions [Working Title]

View full text Add to dashboard Cite

The intestinal protozoan parasites pose serious health concerns, infecting more than one billion individuals every year and mainly causing diarrhea in infants and adults. Main pathogens include Giardia intestinalis, Entamoeba histolytica, Cyclospora cayetanensis, and Cryptosporidium spp. causing giardiasis, amoebiasis, cyclosporiasis, and cryptosporidiosis, respectively. The drug arsenal to treat these diseases is limited (<25 drugs are in clinical use) for the treatment of all protozoal infections. The existing treatment options are decades of years old (discovered in 1930–1980s) and have limitations such as low therapeutic index, toxic side effects during long-term treatment, and drug resistance. Therefore, urgent renewed drug discovery efforts are needed to tackle these neglected protozoal diseases. This chapter discusses the current status of treatment options and their limitations, along with current drug discovery efforts. We conclude that the knowledge gained in the genomic and post-genomic era should be appropriately harnessed to accelerate the futuristic drug discovery process in this field.

show abstract

Section: Recent Drug Discovery Efforts Against Giardiasismentioning

confidence: 99%

Perspectives on the drug discovery of intestinal protozoan parasites

Thakur,

Sharma,

Negi

et al. 2024

Intestinal Parasites - New Developments in Diagnosis, Treatment, Prevention and Future Directions [Working Title]

View full text Add to dashboard Cite

show abstract

“…Additionally, certain derivatives have shown an ability to inhibit the adhesion of the trophozoite to the substrate. This action is particularly interesting as the pathogenicity of the protozoan largely relies on its capacity to adhere to the surface of intestinal epithelial cells [ 92 , 93 ].…”

Section: New Compoundsmentioning

confidence: 99%

Ultrastructural Alterations of the Human Pathogen Giardia intestinalis after Drug Treatment

2023

View full text Add to dashboard Cite

This review presents the main cell characteristics altered after in vitro incubation of the parasite with commercial drugs used to treat the disease caused by Giardia intestinalis. This important intestinal parasite primarily causes diarrhea in children. Metronidazole and albendazole are the primary compounds used in therapy against Giardia intestinalis. However, they provoke significant side effects, and some strains have developed resistance to metronidazole. Benzimidazole carbamates, such as albendazole and mebendazole, have shown the best activity against Giardia. Despite their in vitro efficacy, clinical treatment with benzimidazoles has yielded conflicting results, demonstrating lower cure rates. Recently, nitazoxanide has been suggested as an alternative to these drugs. Therefore, to enhance the quality of chemotherapy against this parasite, it is important to invest in developing other compounds that can interfere with key steps of metabolic pathways or cell structures and organelles. For example, Giardia exhibits a unique cell structure called the ventral disc, which is crucial for host adhesion and pathogenicity. Thus, drugs that can disrupt the adhesion process hold promise for future therapy against Giardia. Additionally, this review discusses new drugs and strategies that can be employed, as well as suggestions for developing novel drugs to control the infection caused by this parasite.

show abstract

Antigiardial Activity of Novel Guanidine Compounds

et al. 2022

View full text Add to dashboard Cite

From four focused compound libraries based on the known anticoccidial agent robenidine, 44 compounds total were synthesised and screened for antigiardial activity. All active compounds were counter-screened for antibiotic and cytotoxic action. Of the analogues examined, 21 displayed IC 50 < 5 μM, seven with IC 50 < 1.0 μM. Most active were 2,2'-bis{ [4-(trifluoromethoxy)phenyl]methylene}carbonimidic dihydrazide hydrochloride (30), 2,2'-bis{[4-(trifluoromethylsulfanyl)phenyl]methylene}carbonimidic dihydrazide hydrochloride (32), and 2,2'-bis[(2-bromo-4,5-dimethoxyphenyl)methylene]carbonimidic dihydrazide hydrochloride ( 41) with IC 50 = 0.2 μM. The maximal observed activity was a 5 h IC 50 value of 0.2 μM for 41. The clinically used metronidazole was inactive at this timepoint at a concentration of 25 μM. Robenidine off-target effects at bacteria and cell line toxicity were removed. Analogue 41 was well tolerated in mice treated orally (100 mg/kg). Following 5 h treatment with 41, no Giardia regrowth was noted after 48 h.

show abstract

Antigiardial Activity of Novel Guanidine Compounds

Cited by 5 publications

References 42 publications

Perspectives on the drug discovery of intestinal protozoan parasites

Perspectives on the drug discovery of intestinal protozoan parasites

Ultrastructural Alterations of the Human Pathogen Giardia intestinalis after Drug Treatment

Antigiardial Activity of Novel Guanidine Compounds

Contact Info

Product

Resources

About