857636-97-6Relevant articles and documents
SMALL MOLECULES INHIBITING TDP-43 ACTIVITY AND USES THEREOF
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Page/Page column 24, (2022/01/24)
The present invention relates to the field of medical pharmacology. In particular, the present invention relates to pharmaceutical agents that serve as inhibitors of the activity of TDP-43. The invention further relates to methods of treatment and / or alleviation of symptoms related to pathological conditions associated with the activity of TDP-43 (for example, neurodevelopmental disorders), comprising the administration to a subject (for example, a human patient) of a composition comprising one or more pharmaceutical agents serving as inhibitors of the activity of TDP-43.
Development of nonsymmetrical 1,4-disubstituted anthraquinones that are potently active against cisplatin-resistant ovarian cancer cells
Pors, Klaus,Plumb, Jane A.,Brown, Robert,Teesdale-Spittle, Paul,Searcey, Mark,Smith, Paul J.,Patterson, Laurence H.
, p. 6690 - 6695 (2007/10/03)
A novel series of 1,4-disubstituted aminoanthraquinones were prepared by ipso-displacement of 1,4-difluoro-5,8-dihydroxyanthraquinones by hydroxylated piperidinyl- or pyrrolidinylalkyl-amino side chains. One aminoanthraquinone (13) was further derivatized to a chloropropyl-amino analogue by treatment with triphenylphosphine-carbon tetrachloride. The compounds were evaluated in the A2780 ovarian cancer cell line and its cisplatin-resistant variants (A2780/cp70 and A2780/MCP1). The novel anthraquinones were shown to possess up to 5-fold increased potency against the cisplatin-resistant cells compared to the wild-type cells. Growth curve analysis of the hydroxyethylaminoanthraquinone 8 in the osteosarcoma cell line U-2 OS showed that the cell cycle is not frozen, rather there is a late cell cycle arrest consistent with the action of a DNA-damaging topoisomerase II inhibitor. Accumulative apoptotic events, using time lapse photography, indicate that 8 is capable of fully engaging cell cycle arrest pathways in G2 in the absence of early apoptotic commitment. 8 and its chloropropyl analogue 13 retained significant activity against human A2780/cp70 xenografted tumors in mice.