Activity of 7-methyljuglone derivatives against Mycobacterium tuberculosis and as subversive substrates for mycothiol disulfide reductase

作者：Mahapatra Anita; Mativandlela Sannah P N; Binneman B; Fourie P B; Hamilton Chris J^*; Meyer J J M; van der Kooy F; Houghton Peter; Lall Namrita

来源：Bioorganic & Medicinal Chemistry, 2007, 15(24): 7638-7646.

DOI：10.1016/j.bmc.2007.08.064

• naphthoquinones
• subversive substrates
• disulfide reductase
• mycothiol
• tuberculosis

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).

• 出版日期2007-12-15