HIV-1; HBV/HCV (EC50 = 0.46μM and 0.15 μM)

Tizoxanide is the active metabolite of Nitazoxanide, which is a thiazolide anti-infective compound against anaerobic bacteria, protozoa, and a range of viruses. IC50 value: Target: Antiviral agent in vitro: Tizoxanide inhibited virus replication of all CIVs with 50% and 90% inhibitory concentrations ranging from 0.17 to 0.21 μM and from 0.60 to 0.76 μM, respectively. Nitazoxanide and its primary metabolite, tizoxanide, inhibit hepatitis C virus (HCV) replication in HCV replicon systems. Interestingly, serial passage in nitazoxanide or tizoxanide resulted in increased sensitivity to alpha interferon 2b: EC(50)s and EC(90)s were reduced three- and eightfold, respectively.

Nitazoxanide is partially effective at reducing the parasite burden in a gnotobiotic piglet diarrhea model when given orally for 11 days at 250 mg/kg/day but not at 125 mg/kg/day. Nitazoxanide induces a drug-related diarrhea in piglets that might have influenced its therapeutic efficacy.

Metabolism / Metabolites
The known metabolites of tezolid include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[2-[(5-nitro-1,3-thiazolyl)carbamoyl]phenoxy]oxacyclohexane-2-carboxylic acid.

[1]. Antimicrob Agents Chemother.1998 Aug;42(8):1959-65.

[2]. Clin Infect Dis.2005 Apr 15;40(8):1173-80.

Desacetazonide belongs to the salicylamide class of drugs. Nitrozonide (NTZ) is a drug currently undergoing human clinical trials to evaluate its efficacy in treating chronic cryptosporidiosis. This study evaluated it in cell culture and two animal models. The inhibitory activity of NTZ was compared with paromomycin (PRM), a partially effective drug against Cryptosporidium parvum. NTZ at a concentration of 10 μg/ml (32 μM) resulted in a sustained reduction of parasite growth of over 90% in cell cultures with almost no drug-related cytotoxicity, while PRM at a concentration of 2000 μg/ml (3.2 mM) only reduced parasite growth by 80%. In contrast to its in vitro efficacy, in SCID mice infected with Cryptosporidium parvum and treated with anti-gamma interferon, NTZ failed to effectively reduce parasite load for 10 consecutive days, regardless of whether the dose was 100 or 200 mg/kg body weight/day. The combined treatment of NTZ and PRM was not superior to the use of PRM alone. In addition, in a germ-free piglet diarrhea model, oral administration of NTZ at 250 mg/kg/day for 11 consecutive days partially reduced the parasite load, while a dose of 125 mg/kg/day was ineffective. However, higher doses of NTZ induced drug-related diarrhea in piglets, which may have affected its therapeutic effect. As we previously reported, PRM at a dose of 500 mg/kg/day significantly reduced the parasite load in piglets. Our results indicate that, among all the tested models, the piglet diarrhea model best simulated the partial response of patients with chronic cryptosporidiosis to nitrozonide (NTZ) treatment. [1] Nitrozonide is a novel thiazole antiparasitic drug that has shown excellent activity against a variety of protozoa and worms in vitro. It is administered orally, has good bioavailability and is well tolerated, with the main side effect being mild gastrointestinal reactions. No drug interactions have been found so far. Nizoralide has been approved for the treatment of Giardia lamblia in patients aged 1 year and older and Cryptosporidium in children aged 1–11 years. It is currently seeking marketing authorization for the treatment of Cryptosporidium infection in adults and for the treatment of immunocompromised patients. It adds an important new member to the antiparasitic drug repertoire. [2]

C10H7N3O4S

265.25

265.015

C, 45.28; H, 2.66; N, 15.84; O, 24.13; S, 12.09

173903-47-4

Tizoxanide-d4;1246817-56-0

394397

Solid powder

1.6±0.1 g/cm3

279-281ºC(dec)

1.750

2.91

2

6

2

18

336

0

S1C(=C([H])N=C1N([H])C(C1=C([H])C([H])=C([H])C([H])=C1O[H])=O)[N+](=O)[O-]

FDTZUTSGGSRHQF-UHFFFAOYSA-N

InChI=1S/C10H7N3O4S/c14-7-4-2-1-3-6(7)9(15)12-10-11-5-8(18-10)13(16)17/h1-5,14H,(H,11,12,15)

2-hydroxy-N-(5-nitrothiazol-2-yl)benzamide

NSC-697856; NSC697856; Tizoxanide; 173903-47-4; 2-hydroxy-N-(5-nitrothiazol-2-yl)benzamide; Benzamide, 2-hydroxy-N-(5-nitro-2-thiazolyl)-; Desacetyl-nitazoxanide; NSC-697856; 2-hydroxy-N-(5-nitro-1,3-thiazol-2-yl)benzamide; UNII-15KFG88UOJ; NSC697856; Tizoxanide; Desacetylnitazoxanide; Desacetyl-nitazoxanide;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~25 mg/mL (~94.25 mM)
Ethanol : < 1 mg/mL

Solubility in Formulation 1: 5 mg/mL (18.85 mM) in 15% Cremophor EL + 85% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication (<60°C).
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 15% Cremophor EL+85% Saline: 5 mg/mL (18.85 mM)

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Solubility in Formulation 3: 5 mg/mL (18.85 mM) in 17% Polyethylene glycol 12-hydroxystearate in Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication (<60°C).
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)