2986-20-1Relevant academic research and scientific papers
Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H4 receptor agonist
Lim, Herman D.,Smits, Rogier A.,Bakker, Remko A.,Van Dam, Cindy M. E.,De Esch, Iwan J. P.,Leurs, Rob
, p. 6650 - 6651 (2006)
During an in-house database screen, we identified S-(2-guanidylethyl)- isothiourea as a high affinity agonist for the histamine H4 receptor, with a 33-fold selectivity over the histamine H3 receptor and negligible affinity for the other histamine receptor subtypes. This nonimidazole ligand is introduced as a useful and complementary pharmacological tool that enables further unraveling of the physiological roles of the H4 receptor.
Synthesis and biological evaluation of 2,4,6-functionalized derivatives of pyrido[2,3-d]pyrimidines as cytotoxic agents and apoptosis inducers
Sanmartin, Carmen,Dominguez, Maria Victoria,Cordeu, Lucia,Cubedo, Elena,Garcia-Foncillas, Jesus,Font, Maria,Palop, Juan Antonio
, p. 28 - 41 (2008/09/21)
In the search for new derivatives with anticancer activity that are able to induce a selective proapoptotic mechanism in cancer cells, we have designed, synthesized, and evaluated a series of new 2-(alkylsulfanyl)-N-alkylpyrido[2,3- d]pyrimidine-4-amine derivatives as cytotoxic and apoptosis inducers. The potential antitumor activity of the compounds was evaluated in vitro by examining their cytotoxic effects against human breast, colon, and bladder cancer-cell lines. The IC50 values of the compounds that showed cytotoxic activity were calculated. The cytotoxic compounds were then tested for their ability to induce caspase-3 activation and nuclear-chromatin degradation. Some compounds, such as 6c, 6d, 6e, 6j, 6o, and 6p, show significant in-vitro cytotoxicity in at least two of the three tested cell lines, induced apoptosis, and also produced a rapid dose-dependent increase in the caspase-3 level in some of the cell lines tested. In order to test the selectivity of the compounds, two non-tumoral human cell lines were used. Several compounds of the did not show cytotoxicity in these cell lines.
Novel potent and selective inhibitors of inducible nitric oxide synthase
Nakane, Masaki,Klinghofer, Vered,Kuk, Jane E.,Donnelly, Jennifer L.,Budzik, Gerald P.,Pollock, Jennifer S.,Basha, Fatima,Carter, George W.
, p. 831 - 834 (2007/10/03)
We have identified two novel potent and selective inhibitors of inducible nitric oxide synthase, S-ethylisothiourea and 2-amino-5,6-dihydro-6-methyl- 4H-1,3-thiazine. K(i) values of 14.7 nM for S-ethylisothiourea and 4.2 nM for 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine were obtained with partially purified preparations of inducible nitric oxide synthase. These compounds demonstrate about 1000-fold greater potency than prototypical inhibitors, and the inhibitions are 10-40-fold more selective for murine inducible nitric oxide synthase, compared with the rat neuronal and bovine endothelial isoforms of nitric oxide synthase. These compounds also potently inhibit the nitric oxide synthase activity in intact J774 mouse macrophages. The inhibition is competitive with the substrate L-arginine and reversible in both enzymatic and intact cell assays. These potent and selective inhibitors of inducible nitric oxide synthase may have potential therapeutic applications in the treatment of inflammatory and autoimmune diseases.
