1228017-66-0Relevant academic research and scientific papers
Stereoselective Modulation of P-Glycoprotein by Chiral Small Molecules
Carocci, Alessia,Catalano, Alessia,Turi, Francesco,Lovece, Angelo,Cavalluzzi, Maria M.,Bruno, Claudio,Colabufo, Nicola A.,Contino, Marialessandra,Perrone, Maria G.,Franchini, Carlo,Lentini, Giovanni
, p. 93 - 101 (2016/01/15)
Inhibition of drug efflux pumps such as P-glycoprotein (P-gp) is an approach toward combating multidrug resistance, which is a significant hurdle in current cancer treatments. To address this, N-substituted aryloxymethyl pyrrolidines were designed and synthesized in their homochiral forms in order to investigate the stereochemical requirements for the binding site of P-gp. Our study provides evidence that the chiral property of molecules could be a strategy for improving the capacity for interacting with P-gp, as the most active compounds of the series stereoselectively modulated this efflux pump. The naphthalene-1-yl analogue (R)-2-[(2,3-dichlorophenoxy)methyl]-1-(naphthalen-1-ylmethyl)pyrrolidine) [(R)-7 a] emerged foremost for its potency and stereoselectivity toward P-gp, with the S enantiomer being nearly inactive. The modulation of P-gp by (R)-7 a involved consumption of ATP, thus demonstrating that the compound behaves as a P-gp substrate.
Chiral aryloxyalkylamines: Selective 5-HT1B/1D activation and analgesic activity
Carocci, Alessia,Lentini, Giovanni,Catalano, Alessia,Cavalluzzi, Maria Maddalena,Bruno, Claudio,Muraglia, Marilena,Colabufo, Nicola Antonio,Galeotti, Nicoletta,Corbo, Filomena,Matucci, Rosanna,Ghelardini, Carla,Franchini, Carlo
scheme or table, p. 696 - 704 (2011/02/22)
A series of chiral 2,3-dichlorophenoxy and 1-naphthyloxy alkylamines were synthesized, and their binding affinities towards 5-HT1D and h5-HT1B receptors were evaluated. In the naphthyloxy series, the (R)-prolinol derivative was the most selective 5-HT1D ligand, while (S)-N-methyl-2-(1-naphthyloxy)propan-1-amine showed the highest selectivity for h5-HT1B. Both compounds performed as 5-HT1D agonists in the isolated guinea pig assay and showed higher analgesic activity than both sumatriptan and the achiral analogue 20b in the mouse hotplate test. Neither ligand displayed any affinity for nicotinic ACh receptors present in mouse brain membranes, thus indicating that their analgesic activity does not arise through interaction with these receptors.
