Symmetrical and unsymmetrical analogues of isoxyl; active agents against Mycobacterium tuberculosis.
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.
Bhowruth
Veemal
V
School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Brown
Alistair K
AK
Reynolds
Robert C
RC
Coxon
Geoffrey D
GD
Mackay
Simon P
SP
Minnikin
David E
DE
Besra
Gurdyal S
GS
D000904:Antibiotics, Antitubercular / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010100:Oxygen / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000737:chemistry / Q000494:pharmacology
D000904:Antibiotics, Antitubercular; D013890:Thiourea; D010100:Oxygen