Symmetrical and unsymmetrical analogues of isoxyl, active against Mycobacterium tuberculosis

Veemal Bhowruth; Alistair Brown; RC Reynolds; GD Coxon; SP Mackay; David Minnikin; Gurdyal Besra

doi:10.1016/j.bmcl.2006.06.095

Symmetrical and unsymmetrical analogues of isoxyl, active against Mycobacterium tuberculosis

Veemal Bhowruth, Alistair Brown, RC Reynolds, GD Coxon, SP Mackay, David Minnikin, Gurdyal Besra

Biosciences

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Abstract

Symmetrical and unsymmetrical analogues of the antimycobacterial agent isoxyl have been synthesized and tested against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG, some showing an increased bactericidal effect. In particular, compounds 1-(p-n-butylphenyl)-3-(4-propoxy-phenyl) thiourea (10) and 1-(p-n-butylphenyl)-3-(4-n-butoxy-phenyl) thiourea (11) showed an approximate 10-fold increase in in vitro potency compared to isoxyl, paralleled by increased inhibition of mycolic acid biosynthesis in M. bovis BCG. Interestingly, these isoxyl analogues showed relatively poor inhibition of oleate production, suggesting that the modifications have changed the spectrum of biological activity.

Original language	English
Pages (from-to)	4743-4747
Number of pages	5
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	16
DOIs	https://doi.org/10.1016/j.bmcl.2006.06.095
Publication status	Published - 15 Sept 2006

Keywords

Mt
isoxyl
Mycobacterium bovis
mycolic acids
inhibitor
Mb
Mycobacterium tuberculosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2006.06.095

The molecular characterisation of the mode of action of the anti-TB agent isoxyl
Besra, D. & Minnikin, D.
Medical Research Council
1/10/05 → 30/09/08
Project: Research Councils

Cite this

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title = "Symmetrical and unsymmetrical analogues of isoxyl, active against Mycobacterium tuberculosis",

abstract = "Symmetrical and unsymmetrical analogues of the antimycobacterial agent isoxyl have been synthesized and tested against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG, some showing an increased bactericidal effect. In particular, compounds 1-(p-n-butylphenyl)-3-(4-propoxy-phenyl) thiourea (10) and 1-(p-n-butylphenyl)-3-(4-n-butoxy-phenyl) thiourea (11) showed an approximate 10-fold increase in in vitro potency compared to isoxyl, paralleled by increased inhibition of mycolic acid biosynthesis in M. bovis BCG. Interestingly, these isoxyl analogues showed relatively poor inhibition of oleate production, suggesting that the modifications have changed the spectrum of biological activity.",

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author = "Veemal Bhowruth and Alistair Brown and RC Reynolds and GD Coxon and SP Mackay and David Minnikin and Gurdyal Besra",

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language = "English",

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journal = "Bioorganic & Medicinal Chemistry Letters",

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T1 - Symmetrical and unsymmetrical analogues of isoxyl, active against Mycobacterium tuberculosis

AU - Bhowruth, Veemal

AU - Brown, Alistair

AU - Reynolds, RC

AU - Coxon, GD

AU - Mackay, SP

AU - Minnikin, David

AU - Besra, Gurdyal

PY - 2006/9/15

Y1 - 2006/9/15

N2 - Symmetrical and unsymmetrical analogues of the antimycobacterial agent isoxyl have been synthesized and tested against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG, some showing an increased bactericidal effect. In particular, compounds 1-(p-n-butylphenyl)-3-(4-propoxy-phenyl) thiourea (10) and 1-(p-n-butylphenyl)-3-(4-n-butoxy-phenyl) thiourea (11) showed an approximate 10-fold increase in in vitro potency compared to isoxyl, paralleled by increased inhibition of mycolic acid biosynthesis in M. bovis BCG. Interestingly, these isoxyl analogues showed relatively poor inhibition of oleate production, suggesting that the modifications have changed the spectrum of biological activity.

AB - Symmetrical and unsymmetrical analogues of the antimycobacterial agent isoxyl have been synthesized and tested against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG, some showing an increased bactericidal effect. In particular, compounds 1-(p-n-butylphenyl)-3-(4-propoxy-phenyl) thiourea (10) and 1-(p-n-butylphenyl)-3-(4-n-butoxy-phenyl) thiourea (11) showed an approximate 10-fold increase in in vitro potency compared to isoxyl, paralleled by increased inhibition of mycolic acid biosynthesis in M. bovis BCG. Interestingly, these isoxyl analogues showed relatively poor inhibition of oleate production, suggesting that the modifications have changed the spectrum of biological activity.

KW - Mt

KW - isoxyl

KW - Mycobacterium bovis

KW - mycolic acids

KW - inhibitor

KW - Mb

KW - Mycobacterium tuberculosis

U2 - 10.1016/j.bmcl.2006.06.095

DO - 10.1016/j.bmcl.2006.06.095

M3 - Article

C2 - 16875817

SN - 0960-894X

VL - 16

SP - 4743

EP - 4747

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

ER -

Symmetrical and unsymmetrical analogues of isoxyl, active against Mycobacterium tuberculosis

Abstract

Keywords

UN SDGs

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The molecular characterisation of the mode of action of the anti-TB agent isoxyl

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