TY - JOUR
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 -
