Symmetrical and unsymmetrical analogues of isoxyl; active agents against mycobacterium tuberculosis

V. Bhowruth; A.K. Brown; R.C. Reynolds; G.D. Coxon; S.P. Mackay; D.E. Minnikin; G.S. Besra

doi:10.1016/j.bmcl.2006.06.095

Symmetrical and unsymmetrical analogues of isoxyl; active agents against mycobacterium tuberculosis

V. Bhowruth, A.K. Brown, R.C. Reynolds, G.D. Coxon, S.P. Mackay, D.E. Minnikin, G.S. Besra

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

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	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2006.06.095
Publication status	Published - 15 Sept 2006

Keywords

Mycobacterium tuberculosis
Mt
Mycobacterium bovis
Mb
mycolic acids
isoxyl
inhibitor

UN SDGs

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

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10.1016/j.bmcl.2006.06.095

Cite this

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title = "Symmetrical and unsymmetrical analogues of isoxyl; active agents 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 = "V. Bhowruth and A.K. Brown and R.C. Reynolds and G.D. Coxon and S.P. Mackay and D.E. Minnikin and G.S. Besra",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Symmetrical and unsymmetrical analogues of isoxyl; active agents against mycobacterium tuberculosis

AU - Bhowruth, V.

AU - Brown, A.K.

AU - Reynolds, R.C.

AU - Coxon, G.D.

AU - Mackay, S.P.

AU - Minnikin, D.E.

AU - Besra, G.S.

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 - Mycobacterium tuberculosis

KW - Mt

KW - Mycobacterium bovis

KW - Mb

KW - mycolic acids

KW - isoxyl

KW - inhibitor

UR - http://www.sciencedirect.com/science/journal/0960894X

UR - http://dx.doi.org/10.1016/j.bmcl.2006.06.095

U2 - 10.1016/j.bmcl.2006.06.095

DO - 10.1016/j.bmcl.2006.06.095

M3 - Article

SN - 0960-894X

VL - 16

SP - 4743

EP - 4747

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 18

ER -

Symmetrical and unsymmetrical analogues of isoxyl; active agents against mycobacterium tuberculosis

Abstract

Keywords

UN SDGs

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