Anti-tumor and anti-angiogenic activity of novel hydantoin derivatives: Inhibition of VEGF secretion in liver metastatic osteosarcoma cells

A series of new azaspiro bicyclic hydantoin derivatives has been designed and synthesized. Initially, the anti-proliferative effect of the hydantoin derivatives was evaluated against human ovarian cancer cells (SKOV-3 and OVSAHO) and murine osteosarcoma cells (LM8 and LM8G7). Among the tested compounds, 8-(3-fluorobenzyl)-1′-(4-(methylsulfonyl)benzyl)-8-azaspiro[bicyclo[3.2.1]octane-3,4′-imidazolidine]-2′,5′-dione (7h) and 8-(3,4-difluorobenzyl)-1′-(4-(methylsulfonyl)benzyl)-8-azaspiro[bicyclo[3.2.1]octane-3,4′-imidazolidine]-2′,5′-dione (7i) showed a significant anti-proliferative activity against the OVSAHO and LM8G7 cells. The real-time monitoring of the effect of the compounds 7h and 7i against the proliferation of LM8G7 was revealed that resulting IC50 values were 102 μM and 13 μM, respectively. We reasoned that the presence of fluorine atom at the 3rd position of the phenyl ring of the hydantoin side chain may determine the potency of the molecule. Furthermore, the compound 7i inhibited the tube formation of the mouse endothelial cells. Finally, the treatment of the compound 7i against the proliferation of LM8G7 cells demonstrated the down regulation of the secretion of VEGF, indicate the potential angioinhibitory effects. In conclusion, our findings demonstrate the suppression of the secretion of VEGF by LM8G7 cells by the compound 7i might contribute at least in part to the antitumor action

Synthesis of Novel 3-Aryl-N-Methyl-1,2,5,6-Tetrahydropyridine Derivatives by Suzuki coupling: As Acetyl Cholinesterase Inhibitors

Alzheimer’s disease (AD) is a neurodegenerative disorder affecting the central nervous system, which is also associated with progressive loss of memory and cognition. The development of numerous structural classes of compounds with different pharmacological profile could be an evolving, promising therapeutic approach for the treatment of AD. Thus, providing a symptomatic treatment for this disease are cholinomimetics with the pharmacological profile of Acetylcholinesterase (AChE) inhibitors. In view of this, we have synthesized novel 3-aryl-N-methyl-1,2,5,6-tetrahydropyridine derivatives 5a-k by Suzuki coupling and screened the efficacy of these derivatives for their AChE inhibitor activity

Synthesis, characterization and evaluation of benzimidazole derivative and its precursors as inhibitors of MDA-MB-231 human breast cancer cell proliferation

10.1016/j.bmcl.2007.08.078Bioorganic and Medicinal Chemistry Letters181432-435BMCL

Synthesis and evaluation of 1-benzhydryl-sulfonyl-piperazine derivatives as inhibitors of MDA-MB-231 human breast cancer cell proliferation

10.1007/s00044-007-9022-yMedicinal Chemistry Research164179-187MCRE

Synthesis and antiproliferative activity of substituted diazaspiro hydantoins: A structure-activity relationship study

10.1007/s10637-008-9150-3Investigational New Drugs272131-139INND

RAD@home citizen science discovery of an AGN spewing a large unipolar radio bubble onto its merging companion galaxy

International audienceAGN feedback during galaxy merger has been the most favoured model to explain black hole-galaxy co-evolution. However, how the AGN-driven jet/wind/radiation is coupled with the gas of the merging galaxies, which leads to positive feedback, momentarily enhanced star formation, and subsequently negative feedback, a decline in star formation, is poorly understood. Only a few cases are known where the jet and companion galaxy interaction leads to minor off-axis distortions in the jets and enhanced star formation in the gas-rich minor companions. Here, we briefly report one extraordinary case, RAD12, discovered by RAD@home citizen science collaboratory, where for the first time a radio jet-driven bubble ~137 kpc is showing a symmetric reflection after hitting the incoming galaxy which is not a gas-rich minor but a gas-poor early-type galaxy in a major merger. Surprisingly, neither positive feedback nor any radio lobe on the counter jet side, if any, is detected. It is puzzling if RAD12 is a genuine one-sided jet or a case of radio lobe trapped, compressed and re-accelerated by shocks during the merger. This is the first imaging study of RAD12 presenting follow-up with the GMRT, archival MeerKAT radio data and CFHT optical data