69844-34-4Relevant articles and documents
Electrochemistry of potentially bioreductive alkylating quinones. Part 4. Qualitative and quantitative structure-activity relationships of aziridinylquinones
Driebergen, R. J.,Moret, E. E.,Janssen, L. H. M.,Beijnen, J. H.,Holthuis, J. J. M.,et al.
, p. 174 - 185 (1993)
The concept of bioreductive alkylation as a mechanism of action of aziridinylquinoid anticancer agents has been investigated.The influence of quinone substituents on quinone reduction, on protonation of the aziridines prior to and following quinone reduction and on partitioning properties of the compound was examined.Parameters obtained from a combined electrochemical, chemical-stability and lipophilicity study describing these processes were determined and correlated quantitatively in a Hansch-type QSAR study with biological data obtained from three experimental tumor models.Poor quantitative correlations between cytotoxicity in a L1210 clonogenic assay and the parameters were obtained.Good linear relationships, however, between antitumor activity in vivo (vs.L1210 leukemic mice and vs.B16 melanoma-bearing mice) and the lipophilic properties of the quinone were found.These relationships, showing a negative correlation between antitumor activity and lipophilicity, can be used to predict the activity of new, unknown compounds.No trend was evident between antitumor activity and other parameters, although some indications for potential importance of electronic and steric properties of the substituents and of their ability to form hydrogen bonds were found.
Dioxonaphthoimidazoliums are Potent and Selective Rogue Stem Cell Clearing Agents with SOX2-Suppressing Properties
Ho, Si-Han Sherman,Ali, Azhar,Ng, Yi-Cheng,Lam, Kuen-Kuen Millie,Wang, Shu,Chan, Woon-Khiong,Chin, Tan-Min,Go, Mei-Lin
supporting information, p. 1944 - 1955 (2016/10/06)
Pluripotent stem cells are uniquely positioned for regenerative medicine, but their clinical potential can only be realized if their tumorigenic tendencies are decoupled from their pluripotent properties. Deploying small molecules to remove remnant undifferentiated pluripotent cells, which would otherwise transform into teratomas and teratomacarcinomas, offers several advantages over non-pharmacological methods. Dioxonapthoimidazolium YM155, a survivin suppressant, induced selective and potent cell death of undifferentiated stem cells. Herein, the structural requirements for stemotoxicity were investigated and found to be closely aligned with those essential for cytotoxicity in malignant cells. There was a critical reliance on the quinone and imidazolium moieties but a lesser dependence on ring substituents, which served mainly to fine-tune activity. Several potent analogues were identified which, like YM155, suppressed survivin and decreased SOX2 in stem cells. The decrease in SOX2 would cause an imbalance in pluripotent factors that could potentially prompt cells to differentiate and hence decrease the risk of aberrant teratoma formation. As phosphorylation of the NF-κB p50 subunit was also suppressed, the crosstalk between phospho-p50, SOX2, and survivin could implicate a causal role for NF-κB signaling in mediating the stem cell clearing properties of dioxonaphthoimidazoliums.
NAPHTHAQUINONE METHYLTRANSFERASE INHIBITORS AND USES THEREOF
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Page/Page column 87; 88; 96, (2015/11/27)
Provided herein are compounds of (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, and prodrugs thereof. Also provided are pharmaceutical compositions and methods involving the inventive compounds for the treatment of proliferative diseases (e.g., cancer (e.g., leukemia, breast cancer, melanoma, metastatic cancer) and diseases associated with inappropriate SET8 activity. Also provided are methods for inhibiting SET8 and methods for labelling SET8.
