1428432-27-2Relevant academic research and scientific papers
Novel inhibitors of bacterial virulence: Development of 5,6-dihydrobenzo[h]quinazolin-4(3H)-ones for the inhibition of group A streptococcal streptokinase expression
Yestrepsky, Bryan D.,Xu, Yuanxi,Breen, Meghan E.,Li, Xiaoqin,Rajeswaran, Walajapet G.,Ryu, Jenny G.,Sorenson, Roderick J.,Tsume, Yasuhiro,Wilson, Michael W.,Zhang, Wenpeng,Sun, Duxin,Sun, Hongmin,Larsen, Scott D.
, p. 1880 - 1897 (2013)
Resistance to antibiotics is an increasingly dire threat to human health that warrants the development of new modes of treating infection. We recently identified 1 (CCG-2979) as an inhibitor of the expression of streptokinase, a critical virulence factor in Group A Streptococcus that endows blood-borne bacteria with fibrinolytic capabilities. In this report, we describe the synthesis and biological evaluation of a series of novel 5,6-dihydrobenzo[h] quinazolin-4(3H)-one analogs of 1 undertaken with the goal of improving the modest potency of the lead. In addition to achieving an over 35-fold increase in potency, we identified structural modifications that improve the solubility and metabolic stability of the scaffold. The efficacy of two new compounds 12c (CCG-203592) and 12k (CCG-205363) against biofilm formation in Staphylococcus aureus represents a promising additional mode of action for this novel class of compounds.
