Exploring ND-011992, a quinazoline-type inhibitor targeting quinone reductases and quinol oxidases.

ABSTRACT: Bacterial energy metabolism has become a promising target for next-generation tuberculosis chemotherapy. One strategy to hamper ATP production is to inhibit the respiratory oxidases. The respiratory chain of Mycobacterium tuberculosis comprises a cytochrome bcc:aa₃ and a cytochrome bd ubiquinol oxidase that require a combined approach to block their activity. A quinazoline-type compound called ND-011992 has previously been reported to ineffectively inhibit bd oxidases, but to act bactericidal in combination with inhibitors of cytochrome bcc:aa₃ oxidase. Due to the structural similarity of ND-011992 to quinazoline-type inhibitors of respiratory complex I, we suspected that this compound is also capable of blocking other respiratory chain complexes. Here, we synthesized

SUBMITTER: Kagi J 

PROVIDER: S-EPMC10382516 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature