1573010-35-1Relevant articles and documents
Defining a minimum pharmacophore for simocyclinone D8 disruption of DNA gyrase binding to DNA
Gaskell, Lauren M.,Nguyen, Thuy,Ellis, Keith C.
, p. 3632 - 3643 (2014/08/05)
The increasing occurrence of drug-resistant bacterial infections in the clinic has created a need for new antibacterial agents. Natural products have historically been a rich source of both antibiotics and lead compounds for new antibacterial agents. The natural product simocyclinone D8 (SD8) has been reported to inhibit DNA gyrase, a validated antibacterial drug target, by a unique catalytic inhibition mechanism of action. In this work, we have used a deconstruction-reconstruction approach to prepare analogs of the coumarin subunit of SD8 and evaluated their ability to disrupt binding of the DNA gyrase enzyme to DNA in a surface plasmon resonance assay. This has led to a minimum pharmacophore required for disruption of binding. Springer Science+Business Media 2014.