868365-72-4Relevant academic research and scientific papers
Inhibitors of apoptosis in lymphocytes: Synthesis and biological evaluation of compounds related to pifithrin-α
Barchéchath, Sylvie D.,Tawatao, Rommel I.,Corr, Maripat,Carson, Dennis A.,Cottam, Howard B.
, p. 6409 - 6422 (2007/10/03)
The chemoprotection of cells from apoptosis induced by toxins or ionizing radiation could be important for biodefense and in the treatment of acute injuries. We describe a series of small heterocycles, including fused benzothiazoles, benzimidazoles, and related compounds, that abrogate thymocyte apoptosis induced by dexamethasone and γ-irradiation. To optimize the protective activity of the previously reported pifithrin-α (PFT-α, 1), various derivatives and analogues of this and the corresponding ring-closed imidazobenzothiazole (IBT, 39) were synthesized. The aromatic analogues of 39 were more protective than 39, while the aromatic analogues of 1 were not active. Compound 19 containing a pyrrolidinyl substituent on the phenyl ring provided potent antiapoptotic activity (EC50 of 1.31 μM compared to 4.16 μM for 1). Modification of aromatic 39 with a pyrrolidinyl para substituent (compound 60) enhanced the activity, lowering the EC50 to 0.35 μM. Also, 60 provided significant protection against γ-irradiation-induced apoptosis, as expected. Compounds 19 and 60 may be promising for potential clinical development.
