174636-75-0Relevant academic research and scientific papers
Design, synthesis and evaluation of quinoline-based small molecule inhibitor of stat3
Shi, Zhi-Bing,Zhang, Lei,Bin, Zheng-Yang,Cao, Xiang-Rong,Gong, Zhu-Nan,Li, Jian-Xin
, p. 420 - 426 (2013/07/26)
As STAT3 has been validated as an anticancer target, its inhibitors have been shown to possess therapeutic promise for the treatment of human cancers. To identify novel and selective STAT3 inhibitors, a virtual screening based on the STAT3 SH2 domain was performed and a small molecule, 2-phenylquinoline-4- carboxylic acid (5a), with an inhibition constant Ki value of 17.53 iM to STAT3 was discovered. On this basis, the derivatives of 5a including esters, amides and dimers were synthesized. The bioactivity and inhibitory selectivity of the derivatives were assayed using human breast cancer cell lines, MDA-MB-468 and MCF-7. Among the derivatives, 5c and 9b showed the most potent inhibitory activity with a good selectivity, and also inhibited STAT3 protein level of MDA-MB-468 cells. The results demonstrated a successful application of virtual screening for lead discovery. Compound 9b might be an effective STAT3 inhibitor lead for the further development of antitumor agents.
Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase
Boa, Andrew N.,Canavan, Shane P.,Hirst, Paul R.,Ramsey, Christopher,Stead, Andrew M.W.,McConkey, Glenn A.
, p. 1945 - 1967 (2007/10/03)
A series of 2-phenyl quinoline-4-carboxylic acid derivatives related to brequinar, an inhibitor of human dihydroorotate dehydrogenase (DHODH), has been prepared and evaluated as inhibitors of DHODH from the malaria parasite Plasmodium falciparum. Brequinar was essentially inactive against PfDHODH (IC50 880 μM) whereas several members of the series inhibited PfDHODH. Unexpectedly, replacement of the carboxylic acid required for brequinar to inhibit hDHODH was not essential in the diisopropylamides that inhibited PfDHODH.
