21333-03-9Relevant academic research and scientific papers
UV365 light promoted catalyst-free synthesis of pyrimido[4,5-b] quinoline-2,4-diones in aqueous-glycerol medium
Nongthombam, Geetmani Singh,Kharmawlong, George Kupar,Kumar, John Elisa,Nongkhlaw, Rishanlang
supporting information, p. 9436 - 9442 (2018/06/18)
Herein, a highly efficient and environmentally benign protocol for the synthesis of biologically important pyrimido[4,5-b]quinolinone-2,4-diones from aromatic amines, barbituric acid and aryl aldehyde is reported. This process takes place at room temperat
Toxoflavins and deazaflavins as the first reported selective small molecule inhibitors of tyrosyl-DNA phosphodiesterase II
Raoof, Ali,Depledge, Paul,Hamilton, Niall M.,Hamilton, Nicola S.,Hitchin, James R.,Hopkins, Gemma V.,Jordan, Allan M.,Maguire, Laura A.,McGonagle, Alison E.,Mould, Daniel P.,Rushbrooke, Mathew,Small, Helen F.,Smith, Kate M.,Thomson, Graeme J.,Turlais, Fabrice,Waddell, Ian D.,Waszkowycz, Bohdan,Watson, Amanda J.,Ogilvie, Donald J.
supporting information, p. 6352 - 6370 (2013/09/23)
The recently discovered enzyme tyrosyl-DNA phosphodiesterase 2 (TDP2) has been implicated in the topoisomerase-mediated repair of DNA damage. In the clinical setting, it has been hypothesized that TDP2 may mediate drug resistance to topoisomerase II (topo II) inhibition by etoposide. Therefore, selective pharmacological inhibition of TDP2 is proposed as a novel approach to overcome intrinsic or acquired resistance to topo II-targeted drug therapy. Following a high-throughput screening (HTS) campaign, toxoflavins and deazaflavins were identified as the first reported sub-micromolar and selective inhibitors of this enzyme. Toxoflavin derivatives appeared to exhibit a clear structure-activity relationship (SAR) for TDP2 enzymatic inhibition. However, we observed a key redox liability of this series, and this, alongside early in vitro drug metabolism and pharmacokinetics (DMPK) issues, precluded further exploration. The deazaflavins were developed from a singleton HTS hit. This series showed distinct SAR and did not display redox activity; however low cell permeability proved to be a challenge.
Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells
Wilson, Jennifer M.,Henderson, Graham,Black, Fiona,Sutherland, Andrew,Ludwig, Robert L.,Vousden, Karen H.,Robins, David J.
, p. 77 - 86 (2007/10/03)
A family of 5-deazaflavin derivatives has been synthesised using a two-step convergent strategy. The biological activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low molecular weight inhibitors of the E3 activity of HMD2 in tumours that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1-3 (HL198C-E)] is not essential for observation of this biological activity.
