AMITHIOZONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H12N4OS
Molecular Weight	236.293
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1

InChI

InChIKey=SRVJKTDHMYAMHA-WUXMJOGZSA-N

InChI=1S/C10H12N4OS/c1-7(15)13-9-4-2-8(3-5-9)6-12-14-10(11)16/h2-6H,1H3,(H,13,15)(H3,11,14,16)/b12-6+

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25552777 | https://www.ncbi.nlm.nih.gov/pubmed/13838487

Amithiozone, also known as thioacetazone, is an oral antibiotic, which is used in the treatment of tuberculosis. In 1991, the World Health Organization (WHO) recommended replacing thioacetazone with ethambutol in patients with known or suspected HIV infection. Thioacetazone is no longer included in WHO’s recommended first-line treatment for tuberculosis and is now reserved for uncommon situations in which treatment options have been compromised by resistance to other anti-tuberculosis medicines in HIV-negative individuals. Despite the increased recognition of this risk, thioacetazone remained in use mainly in low-income countries because of its low cost. Amithiozone has also been used in trials studying the treatment of Mycobacterium Avium-intracellular Infection. One of the possible mechanism action of the drug is interference with the metabolism of methionine of susceptible tubercle bacilli, which utilize methionine for nucleic acid synthesis.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Purine metabolism 1 Target ID: map00230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/13838487	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tuberculosis 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25552777	Curative		Not Provided 504	Unknown Approved Use Unknown
Mycobacterium avium-intracellulare infection 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00004689	Curative		Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
The chemical approach to the control of tuberculosis.	1952 Aug 8	14950210
Antibacterial nitrofuran derivatives. I. 5-nitro-2-furaldehyde semicarbazones and thiosemicarbazones.	1967 Jul	4962510
Protein synthesis in Mycobacterium tuberculosis H37Rv and the effect of streptomycin in streptomycin-susceptible and -resistant strains.	1973 Sep	4202339
The early bactericidal activity of drugs in patients with pulmonary tuberculosis.	1980 Jun	6774638
Aplastic anaemia associated with anti-tuberculosis chemotherapy.	1982	6184934
Thiacetazone: in vitro activity against Mycobacterium avium and M. tuberculosis.	1990 Dec	1702564
The Garrod Lecture. Understanding the chemotherapy of tuberculosis--current problems.	1992 May	1624388
Antituberculosis activity of clarithromycin.	1995 Dec	8593004
Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium.	1997 May	9145860
Green fluorescent protein reporter microplate assay for high-throughput screening of compounds against Mycobacterium tuberculosis.	1998 Feb	9527783
Use of genomics and combinatorial chemistry in the development of new antimycobacterial drugs.	2000 Feb 1	10609550
In vitro activity of thiacetazone on mycobacterial species belonging to the Mycobacterium tuberculosis complex.	2002 Oct	12365582
Activities of moxifloxacin alone and in combination with other antimicrobial agents against multidrug-resistant Mycobacterium tuberculosis infection in BALB/c mice.	2003 Jan	12499213
Clinical concentrations of thioridazine kill intracellular multidrug-resistant Mycobacterium tuberculosis.	2003 Mar	12604522
Differential antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates.	2005 Nov	16251329
EthA, a common activator of thiocarbamide-containing drugs acting on different mycobacterial targets.	2007 Mar	17220416
Preclinical pharmacokinetics of KBF611, a new antituberculosis agent in mice and rabbits, and comparison with thiacetazone.	2010 Mar	20038272
A common mechanism of inhibition of the Mycobacterium tuberculosis mycolic acid biosynthetic pathway by isoxyl and thiacetazone.	2012 Nov 9	23002234

Patents

Sample Use Guides

In Vivo Use Guide

150 mg daily doses 6 days a week over the entire treatment period for a total of 8 months.

Route of Administration: Oral

In Vitro Use Guide

Fifty-four strains of M. tuberculosis complex were characterised based on the minimum inhibitory concentration (MIC) of thiacetazone (amithiozone) and the growth pattern in the presence of different concentrations of the drug. The results showed that the MIC of thiacetazone to type II M. africanum strains was significantly higher than for other strains in the study (P < 0.01). Thiacetazone showed a paradoxical effect on 63% of strains where lower concentrations exhibited a better inhibiting activity than higher concentrations.

Name

Type

Language

AMITHIOZONE

Common Name

English

N-(4-(((AMINO-THIOXOMETHYL)HYDRAZONO)METHYL)PHENYL)ACETAMIDE [WHO-IP]

Systematic Name

English

CITAZONE

Brand Name

English

THIOACETAZONE

Official Name

English

4'-FORMYLACETANILIDE THIOSEMICARBAZONE

Systematic Name

English

THIOPARAMIZONE

Common Name

English

Thioacetazone [WHO-DD]

Common Name

English

THIOACETAZONUM [WHO-IP LATIN]

Common Name

English

THIOACETAZONE [MART.]

Common Name

English

THIOACETAZONE [WHO-IP]

Common Name

English

thioacetazone [INN]

Common Name

English

THIOCARBAZIL

Brand Name

English

THIACETAZONE

Common Name

English

NSC-3550

Code

English

THIBONE

Common Name

English

SQ-2321

Code

English

TB I-698

Code

English

THIACETAZONE [MI]

Common Name

English

4-ACETAMIDOBENZALDEHYDE THIOSEMICARBAZONE

Systematic Name

English

P-ACETAMIDOBENZALDEHYDE THIOSEMICARBAZONE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C280