Predicting hiCE inhibitors based upon pharmacophore models derived from the receptor and its ligands

Human intestinal carboxyl esterase (hiCE) is a drug target for ameliorating irinotecan-induced diarrhea. By reducing irinotecan-induced diarrhea, hiCE inhibitors can improve the anti-cancer efficacy of irinotecan. To find effective hiCE inhibitors, a new virtual screening protocol that combines pharmacophore models derived from the hiCE structure and its ligands has been proposed. The hiCE structure has been constructed through homology techniques using hCES1’s crystal structure. The hiCE structure was optimized via molecular dynamics simulations with the most known active hiCE inhibitors docked into the structure. An optimized pharmacophore, derived from the receptor, was then generated. A ligand-based pharmacophore was also generated from a larger set of known hiCE inhibitors. The final hiCE inhibitor predictions were based upon the virtual screening hits from both ligand-based and receptor-based pharmacophore models. The hit rates from the ligand-based and receptor-based pharmacophore models are 88% and 86%, respectively. The final hit rate is 94%. The two models are highly consistent with one another (85%). This proves that both models are reliable.     

Highly selective synthesis of single-walled carbon nanotubes from methane in a coupled Downer-turbulent fluidized-bed reactor

For the synthesis of single-walled carbon nanotubes (SWCNTs) from CH₄ over a Fe/MgO catalyst, we proposed a coupled Downer-turbulent fluidized-bed (TFB) reactor to enhance the selectivity and yield (or production rate) of SWCNTs. By controlling a very short catalyst residence time (1–3 s) in the Downer, only part of Fe oxides can be reduced to form Fe nano particles (NPs) available for the growth of SWCNTs. The percentage of unreduced Fe oxides increased and the yield of SWCNTs decreased accordingly with the increase of catalyst feeding rate in Downer. SWCNTs were preferentially grown on the catalyst surface and inhibited the sintering of the Fe crystallites which would be formed thereafter in the downstream TFB, evidenced by TEM, Raman and TGA. The coupled Downer-turbulent fluidized-bed reactor technology allowed higher selectivity and higher production rate of SWCNTs as compared to TFB alone.     

Simple and Efficient Synthesis of Belinostat

A novel synthesis of belinostat (1) starting from 3-nitrobenzaldehyde has been developed. The key step in this sequence involves the conversion of (2E)-3-(3-aminophenyl)acrylic acid methyl ester to (2E)-3-(3-chlorosulfonylphenyl)acrylic acid methyl ester via diazotization and sulfonylation.     

Asymmetric Inductive Synthesis of α-Aminoaryl-Acetic Acids in Chiral Micellar System

In the micellar solution of chiral surfactant N-hexadecyl-N-methylephedrine bromide, seven α-amino-arylacetic acids were synthesized from corresponding aldehydes, the e.e.% being about 28%.     

Carbon-Carbon Bond Formation Reaction Promoted by Cadmium In Aqueous Media

Promoted by metallic cadmium allylilic and propargyl bromides react smoothly with aldehydes in aqueous DMF to give homoallylic and homopropargyl alcohols in moderate to good yields. It can also promote pinacol coupling of aromatic aldehydes. The metallic cadmium is produced in situ by the reduction of CdCl₂ H₂O with samarium metal.     

Wang Resin Bound Addition Reactions Under Microwave Irradiation

The addition reaction process of Wang resin bound amines with isocyanates was monitored directly using a FTIR method. It showed that the reaction process was greatly enhanced under microwave irradiation.