1428474-90-1Relevant academic research and scientific papers
Ionic liquid mediated synthesis of mono- and bis-spirooxindole- hexahydropyrrolidines as cholinesterase inhibitors and their molecular docking studies
Kia, Yalda,Osman, Hasnah,Kumar, Raju Suresh,Basiri, Alireza,Murugaiyah, Vikneswaran
, p. 1318 - 1328 (2014/03/21)
One pot, three-component reaction of 1-acryloyl-3,5- bisarylmethylidenepiperidin-4-ones with isatin and sarcosine in molar ratios of 1:1:1 and 1:2:2 furnished to mono- and bis-spiropyrrolidine heterocyclic hybrids comprising functionalized piperidine, pyrrolidine and oxindole structural motifs. Both mono and bis-spiropyrrolidines displayed good inhibitory activity against acetylcholinesterase (AChE) with IC50 values of 2.36-9.43 μM. For butyrylcholinesterase (BChE), mono-cycloadducts in series 8 with IC50 values of lower than 10 μM displayed better inhibitory activities than their bis-cycloadduct analogs in series 9 with IC50 values of 7.44-19.12 μM. The cycloadducts 9j and 8e were found to be the most potent AChE and BChE inhibitors with IC50 values of 2.35 and 3.21 μM, respectively. Compound 9j was found to be competitive inhibitor of AChE while compound 8e was a mixed-mode inhibitor of BChE with calculated K i values of 2.01 and 6.76 μM, respectively. Molecular docking on Torpedo californica AChE and human BChE showed good correlation between IC 50 values and free binding energy values of the synthesized compounds docked into the active site of the enzymes.
Synthesis and discovery of novel piperidone-grafted mono- and bis-spirooxindole-hexahydropyrrolizines as potent cholinesterase inhibitors
Kia, Yalda,Osman, Hasnah,Kumar, Raju Suresh,Murugaiyah, Vikneswaran,Basiri, Alireza,Perumal, Subbu,Wahab, Habibah A.,Bing, Choi Sy
, p. 1696 - 1707 (2013/05/08)
Three-component reaction of a series of 1-acryloyl-3,5- bisbenzylidenepiperidin-4-ones with isatin and l-proline in 1:1:1 and 1:2:2 molar ratios in methanol afforded, respectively the piperidone-grafted novel mono- and bisspiro heterocyclic hybrids comprising functionalized piperidine, pyrrolizine and oxindole ring systems in good yields. The in vitro evaluation of cholinesterase enzymes inhibitory activity of these cycloadducts disclosed that monospiripyrrolizines (8a-k), are more active with IC50 ranging from 3.36 to 20.07 μM than either the dipolarophiles (5a-k) or bisspiropyrrolizines (9a-k). The compounds, 8i and 8e with IC50 values of 3.36 and 3.50 μM, respectively showed the maximum inhibition of acethylcholinesterase (AChE) and butrylylcholinestrase (BuChE). Molecular modeling simulation, disclosed the binding interactions of the most active compounds to the active site residues of their respective enzymes. The docking results were in accordance with the IC50 values obtained from in vitro cholinesterase assay.
A facile chemo-, regio- and stereoselective synthesis and cholinesterase inhibitory activity of spirooxindole-pyrrolizine-piperidine hybrids
Kia, Yalda,Osman, Hasnah,Kumar, Raju Suresh,Murugaiyah, Vikneswaran,Basiri, Alireza,Perumal, Subbu,Razak, Ibrahim Abdul
, p. 2979 - 2983 (2013/06/26)
A series of novel hybrid spiro heterocycles comprising pyrrolizine, spiroxindole and piperidine moieties was synthesized chemo-, regio- and stereoselectively in good yields from 1,3-dipolar cycloaddition reaction of a series of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with azomethine ylides generated in situ from 5-choloroisatin and l-proline in methanol. These cycloadducts displayed significant cholinesterase inhibitory activity. Among the compounds screened, 8g and 8e, showed maximum inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinestrase (BChE) with IC50 values of 3.33 and 3.13 μM, respectively.
