Activation of 2,4-diaminoquinazoline in Mycobacterium tuberculosis by Rv3161c, a putative dioxygenase

Melief, E.; Bonnett, S. A.; Zuniga, E. S.; Parish, T.

doi:10.1101/375519

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bioRxiv · 10.1101/375519

Activation of 2,4-diaminoquinazoline in Mycobacterium tuberculosis by Rv3161c, a putative dioxygenase

Melief, E.·Bonnett, S. A.·Zuniga, E. S.·Parish, T.

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Abstract

The diaminoquinazoline series has good potency against Mycobacterium tuberculosis. Resistant isolates have mutations in Rv3161c, a putative dioxygenase. We carried out metabolite analysis on wild-type and an Rv3161c mutant strain after exposure to a diaminoquinazoline. The parental compound was found in intracellular extracts from the mutant, but not the wild-type. A metabolite consistent with a mono-hydroxylated form was identified in the wild-type. These data support the hypothesis that Rv3161c metabolizes diaminoquinazolines in M. tuberculosis.

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Melief, E., Bonnett, S. A., Zuniga, E. S., Parish, T.. 2018-07-24. Activation of 2,4-diaminoquinazoline in Mycobacterium tuberculosis by Rv3161c, a putative dioxygenase. https://doi.org/10.1101/375519

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