WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H317852
CAS#: 452-35-7
Description: Ethoxzolamide is an anhydrase carbonic inhibitor. Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence. Ethoxzolamide inhibits PhoPR-regulated genes in infected macrophages and mouse lungs. Moreover, ethoxzolamide reduces M. tuberculosis growth in both macrophages and infected mice. Ethoxzolamide inhibits M. tuberculosis carbonic anhydrase activity.
Hodoodo Cat#: H317852
Name: Ethoxzolamide
CAS#: 452-35-7
Chemical Formula: C9H10N2O3S2
Exact Mass: 258.01
Molecular Weight: 258.317
Elemental Analysis: C, 41.85; H, 3.90; N, 10.84; O, 18.58; S, 24.83
Synonym: Ethoxzolamide, Ethoxyzolamide, Ethoxazolamide, Cardrase, Ethamide; Redupresin; L-643786; 6-Ethoxyzolamide
IUPAC/Chemical Name: 6-ethoxy-1,3-benzothiazole-2-sulfonamide
InChi Key: OUZWUKMCLIBBOG-UHFFFAOYSA-N
InChi Code: InChI=1S/C9H10N2O3S2/c1-2-14-6-3-4-7-8(5-6)15-9(11-7)16(10,12)13/h3-5H,2H2,1H3,(H2,10,12,13)
SMILES Code: O=S(C1=NC2=CC=C(OCC)C=C2S1)(N)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Ethoxzolamide is a carbonic anhydrase inhibitor with Ki of 1 nM. |
| In vitro activity: | To enhance this study’s understanding of its bactericidal properties, this study assessed time-dependent killing kinetics at concentrations corresponding to 1 × MBC and 2 × MBC. For both strains, 99.9% of cells were killed following a 36-h exposure to 2 × MBC of EZA (Fig. 1a, b). When 1 × MBC of EZA was used, 42 h and 48 h were required to kill 99.9% of SS1 (Fig. 1b) and 26695 cells (Fig. 1a), respectively. The DMSO solvent (1% control) had no detectable effect on cell viability under the experimental conditions (Figs. 1a, b). This analysis has also shown that bactericidal activity of EZA against both strains is concentration-dependent. Reference: Gut Pathog. 2020; 12: 20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158114/ |
| In vivo activity: | In contrast, ETZ (Ethoxzolamide) strongly downregulated GFP reporter fluorescence in mouse lungs, with 3-fold inhibition of GFP signal compared to that in the mock-treated control (Fig. 6B). The effect of ETZ treatment on bacterial survival in vivo was also examined. This study observed a significant 0.72-log reduction of bacterial survival in the lungs of ETZ-treated mice compared to the mock-treated control (Fig. 6C). Therefore, adequate ETZ exposure was achieved in mouse lungs to repress the PhoPR regulon and attenuate virulence. Together, these data support that ETZ functions by an antivirulence mechanism and attenuates M. tuberculosis virulence in vivo by (i) targeting M. tuberculosis inside macrophages and the mouse lung, (ii) downregulating the PhoPR regulon, and (iii) reducing the expression of virulence pathways, such as lipid metabolism and Esx-1 secretion. Reference: Antimicrob Agents Chemother. 2015 Aug; 59(8): 4436–4445. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505220/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 387.12 |
The following data is based on the product molecular weight 258.32 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Rahman MM, Tikhomirova A, Modak JK, Hutton ML, Supuran CT, Roujeinikova A. Antibacterial activity of ethoxzolamide against Helicobacter pylori strains SS1 and 26695. Gut Pathog. 2020 Apr 15;12:20. doi: 10.1186/s13099-020-00358-5. PMID: 32318117; PMCID: PMC7158114. 2. Johnson BK, Colvin CJ, Needle DB, Mba Medie F, Champion PA, Abramovitch RB. The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence. Antimicrob Agents Chemother. 2015 Aug;59(8):4436-45. doi: 10.1128/AAC.00719-15. Epub 2015 May 18. PMID: 25987613; PMCID: PMC4505220. |
| In vitro protocol: | 1. Rahman MM, Tikhomirova A, Modak JK, Hutton ML, Supuran CT, Roujeinikova A. Antibacterial activity of ethoxzolamide against Helicobacter pylori strains SS1 and 26695. Gut Pathog. 2020 Apr 15;12:20. doi: 10.1186/s13099-020-00358-5. PMID: 32318117; PMCID: PMC7158114. 2. Johnson BK, Colvin CJ, Needle DB, Mba Medie F, Champion PA, Abramovitch RB. The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence. Antimicrob Agents Chemother. 2015 Aug;59(8):4436-45. doi: 10.1128/AAC.00719-15. Epub 2015 May 18. PMID: 25987613; PMCID: PMC4505220. |
| In vivo protocol: | 1. Johnson BK, Colvin CJ, Needle DB, Mba Medie F, Champion PA, Abramovitch RB. The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence. Antimicrob Agents Chemother. 2015 Aug;59(8):4436-45. doi: 10.1128/AAC.00719-15. Epub 2015 May 18. PMID: 25987613; PMCID: PMC4505220. |
1: Ciocci Pardo A, González Arbeláez LF, Fantinelli JC, Álvarez BV, Mosca SM, Swenson ER. Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia-reperfusion. Physiol Rep. 2021 Nov;9(22):e15093. doi: 10.14814/phy2.15093. PMID: 34806317; PMCID: PMC8606860.
2: Rahman MM, Tikhomirova A, Modak JK, Hutton ML, Supuran CT, Roujeinikova A. Antibacterial activity of ethoxzolamide against Helicobacter pylori strains SS1 and 26695. Gut Pathog. 2020 Apr 15;12:20. doi: 10.1186/s13099-020-00358-5. PMID: 32318117; PMCID: PMC7158114.
3: Modak JK, Tikhomirova A, Gorrell RJ, Rahman MM, Kotsanas D, Korman TM, Garcia-Bustos J, Kwok T, Ferrero RL, Supuran CT, Roujeinikova A. Anti-Helicobacter pylori activity of ethoxzolamide. J Enzyme Inhib Med Chem. 2019 Dec;34(1):1660-1667. doi: 10.1080/14756366.2019.1663416. PMID: 31530039; PMCID: PMC6759998.
4: Kazokaitė J, Aspatwar A, Kairys V, Parkkila S, Matulis D. Fluorinated benzenesulfonamide anticancer inhibitors of carbonic anhydrase IX exhibit lower toxic effects on zebrafish embryonic development than ethoxzolamide. Drug Chem Toxicol. 2017 Jul;40(3):309-319. doi: 10.1080/01480545.2016.1223095. Epub 2016 Sep 6. PMID: 27600313.
5: Johnson BK, Colvin CJ, Needle DB, Mba Medie F, Champion PA, Abramovitch RB. The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence. Antimicrob Agents Chemother. 2015 Aug;59(8):4436-45. doi: 10.1128/AAC.00719-15. Epub 2015 May 18. PMID: 25987613; PMCID: PMC4505220.
6: Gao S, Zhao J, Yin T, Ma Y, Xu B, Moore AN, Dash PK, Hu M. Development and validation of an UPLC-MS/MS method for the quantification of ethoxzolamide in blood, brain tissue, and bioequivalent buffers: applications to absorption, brain distribution, and pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Apr 1;986-987:54-9. doi: 10.1016/j.jchromb.2015.01.034. Epub 2015 Feb 7. PMID: 25706567; PMCID: PMC4507571.
7: Pilipuitytė V, Matulis D. Intrinsic thermodynamics of trifluoromethanesulfonamide and ethoxzolamide binding to human carbonic anhydrase VII. J Mol Recognit. 2015 Mar;28(3):166-72. doi: 10.1002/jmr.2404. Epub 2015 Feb 3. PMID: 25652363.
8: García-Fernández MJ, Tabary N, Martel B, Cazaux F, Oliva A, Taboada P, Concheiro A, Alvarez-Lorenzo C. Poly-(cyclo)dextrins as ethoxzolamide carriers in ophthalmic solutions and in contact lenses. Carbohydr Polym. 2013 Nov 6;98(2):1343-52. doi: 10.1016/j.carbpol.2013.08.003. Epub 2013 Aug 6. PMID: 24053812.
9: Baranauskienė L, Matulis D. Intrinsic thermodynamics of ethoxzolamide inhibitor binding to human carbonic anhydrase XIII. BMC Biophys. 2012 Jun 7;5:12. doi: 10.1186/2046-1682-5-12. PMID: 22676044; PMCID: PMC3534288.
10: Ribeiro A, Sosnik A, Chiappetta DA, Veiga F, Concheiro A, Alvarez-Lorenzo C. Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy. J R Soc Interface. 2012 Sep 7;9(74):2059-69. doi: 10.1098/rsif.2012.0102. Epub 2012 Apr 4. PMID: 22491977; PMCID: PMC3405752.
11: Zubrienė A, Matulienė J, Baranauskienė L, Jachno J, Torresan J, Michailovienė V, Cimmperman P, Matulis D. Measurement of nanomolar dissociation constants by titration calorimetry and thermal shift assay - radicicol binding to Hsp90 and ethoxzolamide binding to CAII. Int J Mol Sci. 2009 Jun 10;10(6):2662-2680. doi: 10.3390/ijms10062662. PMID: 19582223; PMCID: PMC2705510.
12: Di Fiore A, Pedone C, Antel J, Waldeck H, Witte A, Wurl M, Scozzafava A, Supuran CT, De Simone G. Carbonic anhydrase inhibitors: the X-ray crystal structure of ethoxzolamide complexed to human isoform II reveals the importance of thr200 and gln92 for obtaining tight-binding inhibitors. Bioorg Med Chem Lett. 2008 Apr 15;18(8):2669-74. doi: 10.1016/j.bmcl.2008.03.023. Epub 2008 Mar 18. PMID: 18359629.
13: Maren TH, Brechue WF, Bar-Ilan A. Relations among IOP reduction, ocular disposition and pharmacology of the carbonic anhydrase inhibitor ethoxzolamide. Exp Eye Res. 1992 Jul;55(1):73-9. doi: 10.1016/0014-4835(92)90094-9. PMID: 1397133.
14: Puscas I, Buzas G. Treatment of duodenal ulcers with ethoxzolamide, an inhibitor of gastric mucosa carbonic anhydrase. Int J Clin Pharmacol Ther Toxicol. 1986 Feb;24(2):97-9. PMID: 3957499.
15: Eller MG, Schoenwald RD, Dixson JA, Segarra T, Barfknecht CF. Topical carbonic anhydrase inhibitors. III: Optimization model for corneal penetration of ethoxzolamide analogues. J Pharm Sci. 1985 Feb;74(2):155-60. doi: 10.1002/jps.2600740210. PMID: 3989684.
16: Lewis RA, Schoenwald RD, Eller MG, Barfknecht CF, Phelps CD. Ethoxzolamide analogue gel. A topical carbonic anhydrase inhibitor. Arch Ophthalmol. 1984 Dec;102(12):1821-4. doi: 10.1001/archopht.1984.01040031479027. PMID: 6548907.
17: Eller MG, Schoenwald RD. Determination of ethoxzolamide in the iris/ciliary body of the rabbit eye by high-performance liquid chromatography: comparison of tissue levels following intravenous and topical administrations. J Pharm Sci. 1984 Sep;73(9):1261-4. doi: 10.1002/jps.2600730918. PMID: 6491947.
18: Barbarino F, Togănel E, Brilinschi C. The effects of acetazolamide and of ethoxzolamide on gastric microcirculation in rats (histochemical study). Ann N Y Acad Sci. 1984;429:601-3. doi: 10.1111/j.1749-6632.1984.tb12395.x. PMID: 6234837.
19: Mewe L. Klinische Untersuchungen zur Anwendung von Ethoxzolamid in der Glaukomtherapie [Clinical tests on the use of ethoxzolamide in glaucoma therapy (author's transl)]. Klin Monbl Augenheilkd. 1978 Sep;173(3):374-8. German. PMID: 750712.
20: Sanders E. Use of sulfonamide carbonic anhydrase inhibitors in treatment of meningococcal carriers: rationale and report of a clinical trial of ethoxzolamide. Am J Med Sci. 1967 Nov;254(5):709-16. doi: 10.1097/00000441-196711000-00017. PMID: 4964385.
