In vitro inhibition of Giardia lamblia and Trichomonas vaginalis growth by bithionol, dichlorophene, and hexachlorophene

Takeuchi, Tsutomu; Kobayashi, S.; Tanabe, Masanobu; Fujiwara, Toru

doi:10.1128/aac.27.1.65

Cited by 17 publications

(5 citation statements)

References 11 publications

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“…A wide variety of chemotherapeutic agents including rifampin, bithionol, dichlorophene, hexachlorophene, pyrimethamine, sodium fusidate, chloroquine, and mefloquine have demonstrated in vitro activity against Giardia (81,84,233). Lipophilic tetracyclines, such as doxycycline, are highly active in vitro; however, their clinical efficacy is limited, perhaps because of their rapid absorption from the intestine (70).…”

Section: Classes Of Agents and Clinical Propertiesmentioning

confidence: 99%

Treatment of Giardiasis

2001

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Giardia lamblia is both the most common intestinal parasite in the United States and a frequent cause of diarrheal illness throughout the world. In spite of its recognition as an important human pathogen, there have been relatively few agents used in therapy. This paper discusses each class of drugs used in treatment, along with their mechanism of action, in vitro and clinical efficacy, and side effects and contraindications. Recommendations are made for the preferred treatment in different clinical situations. The greatest clinical experience is with the nitroimidazole drugs, i.e., metronidazole, tinidazole, and ornidazole, which are highly effective. A 5- to 7-day course of metronidazole can be expected to cure over 90% of individuals, and a single dose of tinidazole or ornidazole will cure a similar number. Quinacrine, which is no longer produced in the United States, has excellent efficacy but may be poorly tolerated, especially in children. Furazolidone is an effective alternative but must be administered four times a day for 7 to 10 days. Paromomycin may be used during early pregnancy, because it is not systematically absorbed, but it is not always effective. Patients who have resistant infection can usually be cured by a prolonged course of treatment with a combination of a nitroimidazole with quinacrine

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Section: Classes Of Agents and Clinical Propertiesmentioning

confidence: 99%

Treatment of Giardiasis

2001

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“…In fact, MN02 is structurally close to the known dichlorophen with the only difference in the position of chloro substitutions. Dichlorophen is a compound used in many veterinary preparations (Gilvydis, ) as anthelmintic agent and antiprotozoal agent (Kawasaki & Takeuchi, ; Takeuchi, Kobayashi, Tanabe, & Fujiwara, ). As the protein target of dichlorophen and its derivatives (i.e., bithionol, bromochlorophen, resorcinol sulfide, and hexachlorophene) has never been reported before, it would be interesting to check the binding potential of these compounds via docking them into the FabI active site.…”

Section: Resultsmentioning

confidence: 99%

Structure‐based drug design and in vitro testing reveal new inhibitors of enoyl‐acyl carrier protein reductases

et al. 2019

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The need for new antibacterial agents is increasingly becoming of great importance as bacterial resistance to current drugs is quickly spreading. Enoyl‐acyl carrier protein reductases (FabI) are important enzymes for fatty acid biosynthesis in bacteria and other micro‐organisms. In this project, we conducted structure‐based virtual screening against the FabI enzyme, and accordingly, 37 compounds were selected for experimental testing. Interestingly, five compounds were able to demonstrate antimicrobial effect with variable inhibition activity against various strains of bacteria and fungi. Minimum inhibitory concentrations of the active compounds were determined and showed to be in low to medium micromolar range. Subsequently, enzyme inhibition assay was carried out for our five antimicrobial hits to confirm their biological target and determine their IC50 values. Three of these tested compounds exhibited inhibition activity for the FabI enzyme where our best hit MN02 had an IC50 value of 7.8 μM. Furthermore, MN02 is a small bisphenolic compound that is predicted to have all required features to firmly bind with the target enzyme. To sum up, hits discovered in this work can act as a good starting point for the future development of new and potent antimicrobial agents.

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“…hexachlorophene (ec 50 = 11 µm; fig. 3A) was previously described as an in vitro growth inhibitor for the protozoans Giardia lamblia and Trichomonas vaginalis 13 via inhibition of two thiol-modifying enzymes: homocysteine disulfurase and serine sulfhydrase. hexachlorophene is also an inhibitor of β-oxoacyl-acp reductase, involved in fatty acid synthesis in liver stage P. falciparum.…”

Section: Resultsmentioning

confidence: 99%

A High-Throughput Turbidometric Assay for Screening Inhibitors of Leishmania major Protein Disulfide Isomerase

Khalaf

Muylder

Ratnam³

et al. 2011

SLAS Discovery

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The use of a high-throughput technique to perform a pilot screen for Leishmania major protein disulfide isomerase (LmPDI) inhibitors identification is reported. In eukaryotic cells, protein disulfide isomerase (PDI) plays a crucial role in protein folding by catalyzing the rearrangement of disulfide bonds in substrate proteins following their synthesis. LmPDI displays similar domain structure organization and functional properties to other PDI family members and is involved in Leishmania virulence. The authors used a method based on the enzyme-catalyzed reduction of insulin in the presence of dithiothreitol. The screen of a small library of 1920 compounds was performed in a 384-well format and led to the identification of 27 compounds with inhibitory activity against LmPDI. The authors further tested the cytotoxicity of these compounds using Jurkat cells as well as their effect on Leishmania donovani amastigotes using high-content analysis. Results show hexachlorophene and a mixture of theaflavin monogallates inhibit Leishmania multiplication in infected macrophages derived from THP-1 cells, although the inhibitory effect on LmPDI enzymatic activity does not necessarily correlate with the antileishmanial activity.

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In vitro inhibition of Giardia lamblia and Trichomonas vaginalis growth by bithionol, dichlorophene, and hexachlorophene

Cited by 17 publications

References 11 publications

Treatment of Giardiasis

Treatment of Giardiasis

Structure‐based drug design and in vitro testing reveal new inhibitors of enoyl‐acyl carrier protein reductases

A High-Throughput Turbidometric Assay for Screening Inhibitors of Leishmania major Protein Disulfide Isomerase

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