Activity of 7-methyljuglone derivatives against Mycobacterium tuberculosis and as subversive substrates for mycothiol disulfide reductase.
The naphthoquinone 7-methyljuglone (5-hydroxy-7-methyl-1,4-naphthoquinone) has previously been isolated and identified as an active component of root extracts of Euclea natalensis which displays antitubercular activity. Herein, a series of synthetic and plant-derived naphthoquinone derivates of the 7-methyljuglone scaffold have been prepared and evaluated for antibacterial activity against Mycobacterium tuberculosis. Several of these compounds have been shown to operate as subversive substrates with mycothiol disulfide reductase. The absence of a direct correlation between antitubercular activity and subversive substrate efficiency with mycothiol disulfide reductase, might be a consequence of their non-specific reactivity with multiple biological targets (e.g. other disulfide reductases).
Mahapatra
Anita
A
Department of Botany, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0002, South Africa.
Mativandlela
Sannah P N
SP
Binneman
B
B
Fourie
P B
PB
Hamilton
Chris J
CJ
Meyer
J J M
JJ
van der Kooy
F
F
Houghton
Peter
P
Lall
Namrita
N
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D031262:Ebenaceae / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D009285:Naphthoquinones / Q000737:chemistry* / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry*
C517013:7-methyljuglone; D000900:Anti-Bacterial Agents; D009285:Naphthoquinones; D009247:NADH, NADPH Oxidoreductases; C089267:disulfide reductase, mycothiol