ABSTRACT
UNLABELLED: Cell proliferation control plays a key role in tumor development. The basic Fibroblast Growth Factor (bFGF), as well as other growth factors, is involved in several pathologies characterized by dysregulation of cell proliferation. In the present work the effects of PD166866, a very potent and selective tyrosine kinase inhibitor were evaluated. Cultured murine fibroblasts (the cell line 3T6) were used to assess the FGFR-1 inhibition mediated by PD166866. Evaluation of cell viability and molecular biology techniques were adopted. PD166866 controls negatively the bFGF/FGFR-1 system thus promoting a significant reduction of cell proliferation and loss of viability in 3T6 cells. The drug possibly controls proliferation via induction of apoptosis as evidenced by a relevant chromatin degradation. CONCLUSION: This study demonstrated that PD166866 might be used in the control of fibrotic proliferative diseases, as well as in other tumor pathologies.
Subject(s)
Cell Proliferation/drug effects , Fibroblast Growth Factor 2/antagonists & inhibitors , Pyrimidines/pharmacology , Urea/analogs & derivatives , Animals , Cell Death , Cell Line, Tumor , Fluorescent Antibody Technique , In Situ Nick-End Labeling , Mice , Proliferating Cell Nuclear Antigen/analysis , Proliferating Cell Nuclear Antigen/metabolism , Pyrimidines/toxicity , Urea/pharmacology , Urea/toxicityABSTRACT
Some 6- and 7-methoxy-(and hydroxy-) tacrine derivatives were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities. The most potent analogue in our series was the 9-heptylamino-6-methoxytacrine 3af which, in comparison with tacrine (THA), displayed an almost identical inhibitory effect, slightly lower acute toxicity and higher selectivity profile towards AchE when compared with THA.
