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BioAssay: AID 613882

Inhibition of Mycobacterium tuberculosis recombinant EphB expressed in Escherichia coli BL21 using CMNPC as substrate at 10 nM after 30 mins by fluorescent assay relative to control

The treatment of tuberculosis is becoming more difficult due to the ever increasing prevalence of drug resistance. Thus, it is imperative that novel anti-tuberculosis agents, with unique mechanisms of action, be discovered and developed. The direct anti-tubercular testing of a small compound library led to discovery of adamantyl urea hit compound 1. In this study, the hit was followed up through more ..
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 Tested Compounds
 Tested Compounds
All(42)
 
 
Inactive(3)
 
 
Unspecified(39)
 
 
 Tested Substances
 Tested Substances
All(42)
 
 
Inactive(3)
 
 
Unspecified(39)
 
 
 Related BioAssays
 Related BioAssays
AID: 613882
Data Source: ChEMBL (763893)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2014-05-26

Data Table ( Complete ):           All
Target
Sequence: PROBABLE EPOXIDE HYDROLASE EPHB (EPOXIDE HYDRATASE) (Epoxide hydrolase)
Description ..   
Comment ..   

     More BioActivity Data..
Tested Compounds:
Description:
Title: The structure-activity relationship of urea derivatives as anti-tuberculosis agents.

Abstract: The treatment of tuberculosis is becoming more difficult due to the ever increasing prevalence of drug resistance. Thus, it is imperative that novel anti-tuberculosis agents, with unique mechanisms of action, be discovered and developed. The direct anti-tubercular testing of a small compound library led to discovery of adamantyl urea hit compound 1. In this study, the hit was followed up through the synthesis of an optimization library. This library was generated by systematically replacing each section of the molecule with a similar moiety until a clear structure-activity relationship was obtained with respect to anti-tubercular activity. The best compounds in this series contained a 1-adamantyl-3-phenyl urea core and had potent activity against Mycobacterium tuberculosis plus an acceptable therapeutic index. It was noted that the compounds identified and the pharmacophore developed is consistent with inhibitors of epoxide hydrolase family of enzymes. Consequently, the compounds were tested for inhibition of representative epoxide hydrolases: M. tuberculosis EphB and EphE; and human soluble epoxide hydrolase. Many of the optimized inhibitors showed both potent EphB and EphE inhibition suggesting the antitubercular activity is through inhibition of multiple epoxide hydrolase enzymes. The inhibitors also showed potent inhibition of humans soluble epoxide hydrolase, but limited cytotoxicity suggesting that future studies must be towards increasing the selectivity of epoxide hydrolase inhibition towards the M. tuberculosis enzymes.
(PMID: 21840723)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Inhibition activity commentInhibition activity commentString
2Inhibition standard flagInhibition standard flagInteger
3Inhibition qualifierInhibition qualifierString
4Inhibition published valueInhibition published valueFloat%
5Inhibition standard valueInhibition standard valueFloat%

Data Table (Concise)
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