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Chemical Structure| 2277-92-1 Chemical Structure| 2277-92-1

Structure of Oxyclozanide
CAS No.: 2277-92-1

Chemical Structure| 2277-92-1

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Oxyclozanide is a salicylanilide anthelmintic drug.

Synonyms: Zanil; Oxiclozanidum; Oxiclozanida

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Product Citations

Product Citations

Reunanen, Saku ; Ghemtio, Leo ; Patel, Jayendrakumar Z ; Patel, Darshitkumar R ; Airavaara, Kerttu ; Yli-Kauhaluoma, Jari , et al.

Abstract: Parkinson's disease (PD) is a common neurodegenerative disease, typically treated with levodopa, which alleviates the motor symptoms of the disease. However, levodopa metabolism in peripheral tissues hampers its bioavailability and leads to undesired side-effects. Therefore, co-administration of amino acid decarboxylase (AADC) inhibitors is necessary, but still, up to 50% of levodopa may not reach the brain. Recent evidence suggests that gut microbes, especially Enterococcus faecalis, are also able to metabolize levodopa and affect the bioavailability by utilizing microbial tyrosine decarboxylase (TyrDC) enzyme. The main aim of this study was to develop inhibitors targeting gut microbial and host decarboxylation of levodopa. First, a virtual screen of a library of 158,000 compounds against E. faecalis TyrDC was conducted, combining three methods: molecular docking against the E. faecalis TyrDC homology model, structurebased pharmacophore model, and shape similarity searches based on levodopa, (AADC inhibitor) and (S)-α-fluoromethyltyrosine (TyrDC inhibitor). A total of 394 compounds were selected and tested in vitro by using a cell-based E. faecalis assay measuring inhibition of levodopa metabolism. Three most active compounds (49-92% inhibition at 100 µM) sharing a similar scaffold and a set of commercially available and in-house synthesized analogs were then assessed against purified TyrDC and AADC enzymes. The IC50 values for the most potent compounds for TyrDC and AADC inhibition were 23 µM / 144 µM (compound 1), 42 µM / 199 µM (compound 2) and 51 µM / 182 µM (compound 3), respectively. These compounds also displayed cytotoxic effects on HeLa cells and modest activity against E. faecalis at the same concentration range. The core structure of the compounds presented here can serve as a starting point for the development of a new inhibitor class against TyrDC and AADC, and offers a promising avenue for personalized PD treatment, particularly for patients with high levels of gut microbes expressing the levodopa metabolizing TyrDC enzyme.

Keywords: Levodopa ; Parkinson's disease ; Gut microbiome ; Tyrosine decarboxylase

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Alternative Products

Product Details of Oxyclozanide

CAS No. :2277-92-1
Formula : C13H6Cl5NO3
M.W : 401.46
SMILES Code : O=C(NC1=CC(Cl)=CC(Cl)=C1O)C2=C(O)C(Cl)=CC(Cl)=C2Cl
Synonyms :
Zanil; Oxiclozanidum; Oxiclozanida
MDL No. :MFCD00864507
InChI Key :JYWIYHUXVMAGLG-UHFFFAOYSA-N
Pubchem ID :16779

Safety of Oxyclozanide

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H319-H332-H372-H400
Precautionary Statements:P260-P264-P270-P273-P280-P301+P312+P330-P304+P312-P305+P351+P338-P314-P337+P313-P391-P501
Class:9
UN#:3077
Packing Group:

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HCT116 cells 20 µM 2 hours Determine the minimal effective concentration for mitochondrial uncoupling, results showed that 20 μM oxyclozanide starts to uncouple mitochondria Cell Death Dis. 2018 Feb 13;9(2):215
MC38 cells 20 µM 2 hours Determine the minimal effective concentration for mitochondrial uncoupling, results showed that 20 μM oxyclozanide starts to uncouple mitochondria Cell Death Dis. 2018 Feb 13;9(2):215
Staphylococcus aureus 100 µM 6 hours To test the killing effect of oxyclozanide on S. aureus biofilms, results showed oxyclozanide alone killed ~90% of S. aureus biofilm cells J Antimicrob Chemother. 2019 Apr 1;74(4):894-906
Pseudomonas aeruginosa PAO1 100 µM 6 hours To assess the ability of oxyclozanide to enhance tobramycin killing of biofilms, results showed the combination was more effective, eradicating 87% of biofilm cells J Antimicrob Chemother. 2019 Apr 1;74(4):894-906

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NSG mice Colon cancer hepatic metastasis model Oral 800 ppm 3 weeks Evaluate the effect of oxyclozanide on colon cancer hepatic metastasis, results showed that oxyclozanide significantly reduced hepatic metastasis Cell Death Dis. 2018 Feb 13;9(2):215

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.49mL

0.50mL

0.25mL

12.45mL

2.49mL

1.25mL

24.91mL

4.98mL

2.49mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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