Browsing by Author "Sheetal"

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Recent developments on the structure–activity relationship studies of MAO inhibitors and their role in different neurological disorders
(Royal Society of Chemistry, 2016) Kumar, Bhupinder; Sheetal; Mantha, Anil K.; Kumar, Vinod
Monoamine oxidase (MAO) enzyme catalyzes the oxidative deamination of xenobiotic and endogenous amines including many neurotransmitters. The MAO enzyme exists in two isoforms; MAO-A and MAO-B and these isoforms display considerable sequence similarity but differ in tissue distribution, inhibitor selectivity and specificity towards ligands. The altered concentration of the neurotransmitters in the brain is linked with the biochemical pathology of various neurological disorders including depression, Alzheimer's disease and Parkinson's disease. MAO inhibitors were the first antidepressants discovered but their irreversible binding to the enzyme resulted in a number of side effects including fatal food–drug interactions. The new generation MAO inhibitors, especially reversible and selective inhibitors, were less toxic and found to be effective against various neurological disorders. Now the MAO enzyme has been recognised as an important drug target and MAO-A selective inhibitors are being developed as drug candidates for the management of depression and anxiety disorders, whereas MAO-B selective inhibitors are found to be effective for the treatment of Parkinson's disease and Alzheimer's disease with a better safety profile as compared to nonselective MAO inhibitors. The current review article describes recent developments on the design, synthesis and screening of MAO inhibitors, structure–activity relationship studies, and their role in the etiology and treatment of various neurological disorders.
Supported-Pd catalyzed tandem approach for N-arylbenzamides synthesis
(Elsevier B.V., 2021-11-21T00:00:00) Sheetal; Sharma, Ajay Kumar; Shaifali; Bhattacherjee, Dhananjay; Sharma, Navneet; Giri, Kousik; Das, Pralay
Aryl iodides as dual arylating agent for C-terminal from oxalic acid [(CO2H)2] and N-terminal from sodium azide (NaN3) for N-aryl benzamides (Ar-CO-NH-Ar) synthesis is a rare invention which has been attempted successfully under this study. A single step tandem approach for the synthesis of N-aryl benzamides has been developed through bifunctional transformation of aryl iodides with in-situ CO from (CO2H)2 and NaN3 following two different pathways of carbonylation and azidation. The polystyrene supported palladium (Pd@PS) catalyst was found to be well compatible to perform the domino-reaction in a double layer vial (DLV) system under base, ligand and additive-free conditions. Moreover, the same approach was further extended with aryl azides for unsymmetric N-aryl benzamides (Ar-CO-NH-Ar') synthesis. Furthermore, the DFT studies were also performed to support the proposed mechanism. � 2021
Synethesis of some piperazine containing scataining scaffolds as potential MAO inhibitors
(Central University of Punjab, 2014) Sheetal; Kumar,Vinod
Ficus benghalensis and Ficus religiosa commonly known as Banyan and Peepal trees (or Bodhi) respectively, are important tropical trees that are being grown and traditionally revered throughout Indian subcontinent for thousands of years; however, DNA sequence-based genetic diversity of these trees are not yet known. In this report, phylogeography of these species using nuclear genome encoded ITS1-5.8S-ITS2 cistron, chloroplast genome encode RPS16- intron and trnL intron, and mitochondrial genome encoded COX1 gene is presented, making this one of the most comprehensive phylogenetic assessment of these trees conducted till date. Phylogeographic analysis of F. religiosa revealed a cryptic species, which later analysis confirmed as a novel species, described in this dissertation as Ficus indoensis Sp. Nov. that indicated affiliation to section Conosycea. Genetic heterogeneity of Ficus benghalensis remained very low and no apparent phylogeographic structures were detected. This study also revealed that colonies of Big Banyan tree at Adyar, Chennai, indeed are clonal, with 100% homology at all four loci investigated. Further, this investigation-having incorporated extensive taxa sampling (n=342) and four unlinked loci- resolved a number of phylogenetic structures within genus Ficus, so far the largest phylogenetic investigation conducted in this genus yet.
Synthesis, biological evaluation and molecular modeling studies of phenyl-/benzhydrylpiperazine derivatives as potential MAO inhibitors.
(Elsevier, 2018) Kumar, Bhupinder; Sheetal; Mantha, Anil K.; Kumar, Vinod
Monoamine oxidase inhibitors (MAOIs) are potential drug candidates for the treatment of various neurological disorders like Parkinson's disease, Alzheimer's disease and depression. In the present study, two series of 4-substituted phenylpiperazine and 1-benzhydrylpiperazine (1-21) derivatives were synthesized and screened for their MAO-A and MAO-B inhibitory activity using Amplex Red assay. Most of the synthesized compounds were found selective for MAO-B isoform except compounds 3, 7, 8, 9 and 13 (MAO-A selective) while compound 11 was non-selective. In the current series, compound 12 showed most potent MAO-B inhibitor activity with IC50 value of 80 nM and compound 7 was found to be most potent MAO-A inhibitor with IC50 value of 120 nM and both the compounds were found reversible inhibitors. Compound 8 was found most selective MAO-A inhibitor while compound 20 was found most selective inhibitor for MAO-B isoform. In the cytotoxicity evaluation, all the compounds were found non-toxic to SH-SY5Y and IMR-32 cells at 25 µM concentration. In the ROS studies, compound 8 (MAO-A inhibitor) reduced the ROS level by 51.2% while compound 13 reduced the ROS level by 61.81%. In the molecular dynamic simulation studies for 30 ns, compound 12 was found quite stable in the active cavity of MAO-B. Thus, it can be concluded that phenyl- and 1-benzhydrylpiperazine derivatives are promising MAO inhibitors and can act as a lead to design potent, and selective MAO inhibitors for the treatment of various neurological disorders.
Synthesis, biological evaluation and molecular modeling studies of phenyl-/benzhydrylpiperazine derivatives as potential MAO inhibitors
(Academic Press Inc., 2018) Kumar, Bhupinder; Sheetal; Mantha, Anil K.; Kumar, Vinod
Monoamine oxidase inhibitors (MAOIs) are potential drug candidates for the treatment of various neurological disorders like Parkinson's disease, Alzheimer's disease and depression. In the present study, two series of 4-substituted phenylpiperazine and 1-benzhydrylpiperazine (1?21) derivatives were synthesized and screened for their MAO-A and MAO-B inhibitory activity using Amplex Red assay. Most of the synthesized compounds were found selective for MAO-B isoform except compounds 3, 7, 8, 9 and 13 (MAO-A selective) while compound 11 was non-selective. In the current series, compound 12 showed most potent MAO-B inhibitor activity with IC50 value of 80 nM and compound 7 was found to be most potent MAO-A inhibitor with IC50 value of 120 nM and both the compounds were found reversible inhibitors. Compound 8 was found most selective MAO-A inhibitor while compound 20 was found most selective inhibitor for MAO-B isoform. In the cytotoxicity evaluation, all the compounds were found non-toxic to SH-SY5Y and IMR-32 cells at 25 ?M concentration. In the ROS studies, compound 8 (MAO-A inhibitor) reduced the ROS level by 51.2% while compound 13 reduced the ROS level by 61.81%. In the molecular dynamic simulation studies for 30 ns, compound 12 was found quite stable in the active cavity of MAO-B. Thus, it can be concluded that phenyl- and 1-benzhydrylpiperazine derivatives are promising MAO inhibitors and can act as a lead to design potent, and selective MAO inhibitors for the treatment of various neurological disorders. ? 2018 Elsevier Inc.