1489263-00-4Relevant academic research and scientific papers
Design, synthesis, biological evaluation and molecular modelling studies of indole glyoxylamides as a new class of potential pancreatic lipase inhibitors
Sridhar,Palawat, Saksham,Paul, Atish T.
, p. 373 - 381 (2019/01/16)
A series of eighteen indole glyoxylamide analogues were synthesized, characterized and evaluated for their pancreatic lipase inhibitory activity. Porcine pancreatic lipase (Type II) was used with 4-nitrophenyl butyrate (as substrate) for the in vitro assay. Compound 8f exhibited competitive inhibition against pancreatic lipase with IC50 value of 4.92 μM, comparable to that of the standard drug, orlistat (IC50 = 0.99 μM). Compounds 7a-i and 8a-i were subjected to molecular docking into the active site of human PL (PDB ID: 1LPB) wherein compound 8f possessed a potential MolDock score of ?153.037 kcal/mol. Molecular dynamics simulation of 8f complexed with pancreatic lipase, confirmed the role of aromatic substitution in stabilizing the ligand through hydrophobic interactions (maximum observed RMSD = 3.5 ?).
Modulation of A2B adenosine receptor by 1-Benzyl-3-ketoindole derivatives
Taliani, Sabrina,Trincavelli, Maria Letizia,Cosimelli, Barbara,Laneri, Sonia,Severi, Elda,Barresi, Elisabetta,Pugliesi, Isabella,Daniele, Simona,Giacomelli, Chiara,Greco, Giovanni,Novellino, Ettore,Martini, Claudia,Da Settimo, Federico
, p. 331 - 337 (2013/10/21)
We have disclosed a series of 1-benzyl-3-ketoindole derivatives acting as either positive or negative modulators of the human A2B adenosine receptor (A2B AR) depending on small differences in their side chain. The new compounds were designed taking into account structural similarities between AR antagonists and ligands of the GABAA/benzodiazepine receptor. All compounds resulted totally inactive at A2A and A 3 ARs and showed small (8a,b) or none (7a,b, 8c and 9a,b) affinity for A1 AR. When tested on A2B AR-transfected CHO cells, 7a,b and 8a acted as positive modulators, whereas 8b,c and 9a,b acted as negative modulators, enhancing or weakening the NECA-induced increase of cAMP levels, respectively. Compounds 7-9 might be regarded as useful biological and pharmacological tools to explore the therapeutic potential of A2B AR modulators, while their 3-ketoindole scaffold might be taken as a reference to design new analogs.
