5443-16-3Relevant articles and documents
Discovery of novel small molecule inhibitors of S100P with in vitro anti-metastatic effects on pancreatic cancer cells
Camara, Ramatoulie,Ogbeni, Deborah,Gerstmann, Lisa,Ostovar, Mehrnoosh,Hurer, Ellie,Scott, Mark,Mahmoud, Nasir G.,Radon, Tomasz,Crnogorac-Jurcevic, Tatjana,Patel, Pryank,Mackenzie, Louise S.,Chau, David Y.S.,Kirton, Stewart B.,Rossiter, Sharon
, (2020/07/23)
S100P, a calcium-binding protein, is known to advance tumor progression and metastasis in pancreatic and several other cancers. Herein is described the in silico identification of a putative binding pocket of S100P to identify, synthesize and evaluate novel small molecules with the potential to selectively bind S100P and inhibit its activation of cell survival and metastatic pathways. The virtual screening of a drug-like database against the S100P model led to the identification of over 100 clusters of diverse scaffolds. A representative test set identified a number of structurally unrelated hits that inhibit S100P-RAGE interaction, measured by ELISA, and reduce in vitro cell invasion selectively in S100P-expressing pancreatic cancer cells at 10 μM. This study establishes a proof of concept in the potential for rational design of small molecule S100P inhibitors for drug candidate development.
Electrostatically Driven CO-πAromatic Interactions
Li, Ping,Vik, Erik C.,Maier, Josef M.,Karki, Ishwor,Strickland, Sharon M. S.,Umana, Jessica M.,Smith, Mark D.,Pellechia, Perry J.,Shimizu, Ken D.
supporting information, p. 12513 - 12517 (2019/09/04)
A series of N-arylimide molecular balances were developed to study and measure carbonyl-aromatic (CO-π) interactions. Carbonyl oxygens were observed to form repulsive interactions with unsubstituted arenes and attractive interactions with electron-deficient arenes with multiple electron-withdrawing groups. The repulsive and attractive CO-πaromatic interactions were well-correlated to electrostatic parameters, which allowed accurate predictions of the interaction energies based on the electrostatic potentials of the carbonyl and arene surfaces. Due to the pronounced electrostatic polarization of the C=O bond, the CO-πaromatic interaction was stronger than the previously studied oxygen-πand halogen-πaromatic interactions.
Synthesis of propellanes containing a bicyclo[2.2.2]octene unit: Via the Diels-Alder reaction and ring-closing metathesis as key steps
Kotha, Sambasivarao,Pulletikurti, Sunil
, p. 14906 - 14915 (2018/04/30)
The synthesis of propellanes containing bicyclo[2.2.2]octene via olefin metathesis approach is less explored. Herein, we describe a simple and convenient method to synthesize propellane derivatives containing a bicyclo[2.2.2]octene unit which are structurally similar to 11β-HSD1 inhibitors by sequential usage of the Diels-Alder reaction, C-allylation and ring-closing metathesis (RCM) as the key steps. Additionally, we expanded this approach to an endo-tricyclo[4.2.2.02,5]decene derivative which is a useful monomer for polymer synthesis and we have also synthesized basketene and anthracene-based propellanes using the same strategy.
