6469-35-8Relevant academic research and scientific papers
Design, synthesis and evaluation of small molecule CD4-mimics as entry inhibitors possessing broad spectrum anti-HIV-1 activity
Curreli, Francesca,Belov, Dmitry S.,Ramesh, Ranjith R.,Patel, Naisargi,Altieri, Andrea,Kurkin, Alexander V.,Debnath, Asim K.
, p. 5988 - 6003 (2016/10/30)
Since our first discovery of a CD4-mimic, NBD-556, which targets the Phe43 cavity of HIV-1 gp120, we and other groups made considerable progress in designing new CD4-mimics with viral entry-antagonist property. In our continued effort to make further progress we have synthesized twenty five new analogs based on our earlier reported viral entry antagonist, NBD-11021. These compounds were tested first in HIV-1 Env-pseudovirus based single-cycle infection assay as well as in a multi-cycle infection assay. Four of these new compounds showed much improved antiviral potency as well as cytotoxicity. We selected two of the best compounds 45A (NBD-14009) and 46A (NBD-14010) to test against a panel of 51 Env-pseudotyped HIV-1 representing diverse subtypes of clinical isolates. These compounds showed noticeable breadth of antiviral potency with IC50of as low as 150 nM. These compounds also inhibited cell-to-cell fusion and cell-to-cell HIV-1 transmission. The study is expected to pave the way of designing more potent and selective HIV-1 entry inhibitors targeted to the Phe43 cavity of HIV-1 gp120.
Synthesis, in vitro and in vivo activity of thiamine antagonist transketolase inhibitors
Thomas, Allen A.,Le Huerou,De Meese,Gunawardana, Indrani,Kaplan, Tomas,Romoff, Todd T.,Gonzales, Stephen S.,Condroski, Kevin,Boyd, Steven A.,Ballard, Josh,Bernat, Bryan,DeWolf, Walter,Han, May,Lee, Patrice,Lemieux, Christine,Pedersen, Robin,Pheneger, Jed,Poch, Greg,Smith, Darin,Sullivan, Francis,Weiler, Solly,Wright, S. Kirk,Lin, Jie,Brandhuber, Barb,Vigers, Guy
, p. 2206 - 2210 (2008/12/20)
Tumor cells extensively utilize the pentose phosphate pathway for the synthesis of ribose. Transketolase is a key enzyme in this pathway and has been suggested as a target for inhibition in the treatment of cancer. In a pharmacodynamic study, nude mice with xenografted HCT-116 tumors were dosed with 1 ('N3′-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium chloride hydrochloride), an analog of thiamine, the co-factor of transketolase. Transketolase activity was almost completely suppressed in blood, spleen, and tumor cells, but there was little effect on the activity of the other thiamine-utilizing enzymes α-ketoglutarate dehydrogenase or glucose-6-phosphate dehydrogenase. Synthesis and SAR of transketolase inhibitors is described.
