198478-03-4Relevant articles and documents
Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer's disease
Meena, Poonam,Nemaysh, Vishal,Khatri, Manisha,Manral, Apra,Luthra, Pratibha Mehta,Tiwari, Manisha
, p. 1135 - 1148 (2015/03/04)
Development of Multi-Target Directed Ligands (MTDLs) has emerged as a promising approach for targeting complex etiology of Alzheimer's disease (AD). Following this approach, a new series of N′-(4-benzylpiperidin-/piperazin-/benzhydrylpiperazin-1-yl)alkylamine derivatives were designed, synthesized and biologically evaluated as inhibitors of cholinesterases (ChEs), amyloid-beta (Aβ) self aggregation and also for their radical scavenging activity. The in vitro studies showed that the majority of synthesized derivatives strongly inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 values in the low-nanomolar range, and were clearly more potent than the reference compound donepezil in this regard. Among them, inhibitors 5h and 5k, strongly inhibited AChE, with IC50 value of 6.83 nM and 2.13 nM, respectively, and particularly, compound 5k was found to be highly selective for AChE (～38-fold). Moreover, both kinetic analysis of AChE inhibition and the docking study suggested that 5k binds simultaneously to catalytic active site and peripheral anionic site of AChE. Besides, these compounds also exhibited greater ability to inhibit self-induced Aβ1-42 aggregation at 25 μM with percentage inhibition from ～54% to 89% and specially compound 5k provided highest inhibition (88.81%). Also, the derivatives containing methoxy and hydroxy groups showed potent oxygen radical absorbance capacity (ORAC) ranging from 2.2- to 4.4-fold of the Trolox value. Furthermore, results of ADMET studies suggested that all compounds exhibited appropriate drug like properties. Taken together, these results suggest that 5k might be a promising lead compound for further AD drug development.
Synthesis, characterization and in vitro biological studies of novel cyano derivatives of N-alkyl and N-aryl piperazine
Chaudhary, Preeti,Nimesh, Surendra,Yadav, Veena,Verma, Akhilesh Kr.,Kumar, Rupesh
, p. 471 - 476 (2008/02/07)
Cyano derivatives of N-alkyl and N-aryl piperazine have been synthesized and screened for antibacterial and antifungal activities. All the synthesized compounds showed the antibacterial activity against pathogenic strains of Staphylococcus aureus (MTCCB 737), Pseudomonas aeruginosa (MTCCB 741), Streptomyces epidermidis (MTCCB 1824) and Escherichia coli (MTCCB 1652) and antifungal activity against pathogenic strains of Aspergillus fumigatus (ITCC 4517), Aspergillus flavus (ITCC 5192) and Aspergillus niger (ITCC 5405). All compounds showed mild to moderate antimicrobial activity. However, compounds 3c, 4a and 6 showed potent antibacterial activity against pathogenic strains used in the study. Compounds 3a, 3b, 4b, and 4d showed mild to moderate antifungal activity against Aspergillus pathogenic strains. The compounds reported in this study were assessed for there cytotoxicity using MTT colorimetric assay on Hela cells. All the compounds showed cell viability more than the control drug gentamicin, with compound 2 having highest i.e. 95% cell viability.
Cu-nanoparticles: A chemoselective catalyst for the aza-Michael reactions of N-alkyl- and N-arylpiperazines with acrylonitrile
Verma, Akhilesh K.,Kumar, Rupesh,Chaudhary, Preeti,Saxena, Amit,Shankar, Ravi,Mozumdar, Subho,Chandra, Ramesh
, p. 5229 - 5232 (2007/10/03)
A novel method for effecting the aza-Michael reactions of N-alkyl- and N-arylpiperazines with acrylonitrile using Cu-nanoparticles is described. The method features the use of 10 mol % Cu (14-17 nm) nanoparticles under mild reaction conditions to afford the addition products in good to excellent yields. The Cu-nanoparticles selectively catalysed the aza-Michael reaction of N-alkyl- and N-arylpiperazines in the presence of aromatic amino or aliphatic hydroxy groups.
