Anti-tubercular derivatives of rhein require activation by the monoglyceride lipase Rv0183.

ABSTRACT: The emergence and perseverance of drug resistant strains of Mycobacterium tuberculosis (Mtb) ensures that drug discovery efforts remain at the forefront of tuberculosis research. There are numerous different approaches that can be employed to lead to the discovery of anti-tubercular agents. In this work, we endeavored to optimize the anthraquinone chemical scaffold of a known drug, rhein, converting it from a compound with negligible activity against Mtb, to a series of compounds with potent activity. Two compounds exhibited low toxicity and good liver microsome stability and were further progressed in attempts to identify the biological target. Whole genome sequencing of resistant isolates revealed inactivating mutations in a monoglyceride lipase. Over-expression tria

SUBMITTER: Abrahams KA 

PROVIDER: S-EPMC7389528 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature