TIOCARLIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H32N2O2S
Molecular Weight	400.577
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)CCOC1=CC=C(NC(=S)NC2=CC=C(OCCC(C)C)C=C2)C=C1

InChI

InChIKey=BWBONKHPVHMQHE-UHFFFAOYSA-N

InChI=1S/C23H32N2O2S/c1-17(2)13-15-26-21-9-5-19(6-10-21)24-23(28)25-20-7-11-22(12-8-20)27-16-14-18(3)4/h5-12,17-18H,13-16H2,1-4H3,(H2,24,25,28)

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Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14559907 | https://www.ncbi.nlm.nih.gov/pubmed/58847 | https://www.ncbi.nlm.nih.gov/pubmed/23002234

Thiocarlide (or tiocarlide or isoxyl) is a drug which was used in the treatment of tuberculosis. In addition was preclinical experiments, which showed, that it purely bacteriostatic against M. leprae. The precise mechanism is still unknown but was shown, that Delta9-desaturase could be a target for it. The more recent experiments have revealed, that Thiocarlide inhibits the dehydration step by the (3R)-hydroxyacyl dehydratases HadAB and HadBC.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Stearoyl-CoA 9-desaturase 1 Target ID: P9WNZ3 Gene ID: 888821.0 Gene Symbol: desA3 Target Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Sources: https://www.ncbi.nlm.nih.gov/pubmed/14559907	Inhibitor 8297
HadAB and/or HadBC 1 Target ID: HadAB and/or HadBC Sources: https://www.ncbi.nlm.nih.gov/pubmed/23002234	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tuberculosis 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/5963588	Curative		Not Provided 504	Unknown Approved Use Unknown
Leprosy 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/58847	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
THE EFFECTIVENESS OF A THIOCARBANILIDE (ISOXYL) AS A THERAPEUTIC DRUG IN MOUSE TUBERCULOSIS.	1963 Nov	14082688
Study of the toxicity of isoxyl. Research on the pathological effects of isoxyl in the rat undergoing chronic experimentation.	1966 Jul	6014841
Thiocarlide (4'4-diisoamyloxythiocarbanilide) blood levels in patients suffering from tuberculosis.	1966 Jun	5963588
Absorption and excretion studies with thiocarlide (4'4-diisoamyloxythiocarbanilide) in man.	1966 Jun	5963587
[Bacteriologic blood level examination in mono-medication with pulverized Isoxyl (diisoamyloxythiocarbanilide)].	1967	5624809
Experimental studies on therapeutic effects of various combinations of antituberculosis drugs. II. Comparison of various regimens in treatment of experimental mouse tuberculosis infected with SM- and INH-resistant Schacht strain.	1967 Jul	4295381
[Simultaneous determination of double labelled isoxyl (3H and 35S) blood levels in man, by radio- and bio-assays].	1968	4974984
Effects of ethionamide and isoxyl on mycolic acid synthesis in Mycobacterium tuberculosis BCG.	1971 Jun	4999216
[Antitubercular agents. 44. N,N-dialkyldithiooxamide].	1988 Nov	3150060
Antimycobacterial activities of isoxyl and new derivatives through the inhibition of mycolic acid synthesis.	1999 May	10223912
Thiolactomycin and related analogues as novel anti-mycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis.	2000 Jun 2	10747933
Unique mechanism of action of the thiourea drug isoxyl on Mycobacterium tuberculosis.	2003 Dec 26	14559907
The use of microarray analysis to determine the gene expression profiles of Mycobacterium tuberculosis in response to anti-bacterial compounds.	2004	15207496
Novel heteroarotinoids as potential antagonists of Mycobacterium bovis BCG.	2004 Feb 12	14761203
Symmetrical and unsymmetrical analogues of isoxyl; active agents against Mycobacterium tuberculosis.	2006 Sep 15	16875817
EthA, a common activator of thiocarbamide-containing drugs acting on different mycobacterial targets.	2007 Mar	17220416
Isoxyl particles for pulmonary delivery: In vitro cytotoxicity and potency.	2010 Aug 30	20600722
A common mechanism of inhibition of the Mycobacterium tuberculosis mycolic acid biosynthetic pathway by isoxyl and thiacetazone.	2012 Nov 9	23002234

Sample Use Guides

In Vivo Use Guide

3 g in tablet form (6 tablets of 0.5 g) repeated after six hours.

Route of Administration: Oral

In Vitro Use Guide

The specific inhibition of oleic acid synthesis by thiocarlide (ISO) suggested that the drug target is the aerobic desaturation system responsible for the synthesis of oleic acid from stearoyl-CoA in mycobacteria. To test this hypothesis Mycobacterium bovis BCG strain was grown in iron-supplemented medium, sonicated, and centrifuged at low speed, and both the cell wall pellet and the supernatant containing both cytosol and plasma membrane were assayed for Δ9 fatty acid desaturase activity. The assay was performed as originally described by Fulco and Bloch with minor modifications. Consistent with the findings of Fulco and Bloch in the absence of NADPH in the assay mixture, no oleic acid was detected. ISO consistently inhibited the incorporation of radioactivity into the oleic acid, but not into stearic acid, by 7% at 0.1 μg/ml and 61% at a concentration of 1.0 μg of ISO/ml in one typical experiment.

Name

Type

Language

TIOCARLIDE

Official Name

English

tiocarlide [INN]

Common Name

English

TIOCARLIDE [MART.]

Common Name

English

DATC

Code

English

NSC-742400

Code

English

TIOCARLIDE [MI]

Common Name

English

4,4'-BIS(ISOPENTYLOXY)THIOCARBANILIDE

Common Name

English

ISOXYL

Common Name

English

THIOCARLIDE

Common Name

English

Tiocarlide [WHO-DD]

Common Name

English

DAT-C

Code

English

Classification Tree Code System Code

WHO-ATC

J04AD02