Abstract:
:Alzheimer's disease, a neurodegenerative disorder continues to be an area of investigation by the international researchers' fraternity. Despite all the ongoing efforts, the effective set of promising cholinesterase inhibitors available in the market for patients' use is limited. Furthermore, the currently available drugs could provide only a palliative type of treatment instead of providing a complete cure or foolproof prevention. Hence, design/discovery of fresh drug molecules as acetylcholinesterase (AChE) inhibitors still remains an urgent requirement. The drug discovery platform, MCULE in the "structure-based virtual screening" (SBVS) mode was used for high throughput ligand screening of over five million structures targeted against the AChE catalytic site. A stepwise query was made for the SBVS input. The number of hits was narrowed down in consecutive succession via varied filtration criteria as AutoDock-Vina rankings, MCULE toxicity filtration, exclusion of ligands having less than four H-bond acceptors, filtration by ΔG cutoff, rule-of-five violation and SWISS ADME profiling. This was followed by holistic analysis of all the results, thereby leading to one promising ligand. The screened out drug molecule, MCULE-5872671137-0-1 exhibited a robust interaction with the AChE catalytic site involving 20 amino acid residues, an acceptable binding free energy of -10.2 kcal/mol in addition to a favorable SWISS ADME-profie showing no harmful effects on the human body. It can be carefully stated that the molecule, MCULE-5872671137-0-1, which is chemically (3S)-N-{4-[(4-chlorophenyl)sulfanyl]phenyl}-3-hydroxypyrrolidine-1-carboxamide could function as a significant "seed" ligand for future design of potent AChE inhibitors and/or novel neuro drugs built upon the seed-scaffold.
journal_name
J Cell Biochemjournal_title
Journal of cellular biochemistryauthors
Shakil Sdoi
10.1002/jcb.28461subject
Has Abstractpub_date
2019-02-11 00:00:00eissn
0730-2312issn
1097-4644pub_type
杂志文章abstract::Giant cell tumor of bone is a progressive, potentially malignant process which destroys skeletal tissue by virtue of its osteoclast complement. As a biological entity it provides a unique natural model of bone resorption by osteoclasts whose recruitment and development is controlled by a neoplastic population of fibro...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章,评审
doi:10.1002/jcb.240550305
更新日期:1994-07-01 00:00:00
abstract::ERK1 and ERK2 share a great deal of homology and have been presumed to have similar functions. Available antibodies recognize both isoforms making the elucidation of functional differences challenging. Mitogen-activated protein (MAP) kinase networks are commonly depicted in the literature as linear and sequential phos...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.25896
更新日期:2017-08-01 00:00:00
abstract::The sex steroid hormones, androgens and estrogens, via their respective nuclear receptors, regulate bone mineral density in humans and mice. Very little is known about the direct targets of the androgen and estrogen receptors in bone cells. First, models of hormone and receptor deficiency in mouse and human bone are d...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章,评审
doi:10.1002/jcb.22970
更新日期:2011-02-01 00:00:00
abstract::Patients with cervical cancer have abnormal cell proliferation and invasion after many years of latency. However, the precise mechanisms remain unclear. Mitogen- and stress-activated kinase 2 (MSK2) is a serine/threonine kinase which displays a phenotype that promotes tumor growth and metastasis in many different type...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.28421
更新日期:2019-02-12 00:00:00
abstract::The retinoblastoma is the most common intraocular malignant tumor in infants and children; it is one of the deadliest forms of cancer due to its limited sensitivity to chemotherapy and radiotherapy. In several cancers, chemoresistance is associated with autophagy induction. Non-coding RNAs, including long non-coding R...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.26464
更新日期:2018-05-01 00:00:00
abstract::The caspase family of protease is speculated to have a crucial role in apoptosis. The effect of treatment with Idarubicin (IDA) and Medroxyprogesterone acetate (MPA), used alone or in combination, on the activation of Caspase-3 in canine Chronic Lymphatic Leukaemia (CLL) cells was investigated, in order to clarify the...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.10556
更新日期:2003-07-01 00:00:00
abstract::Receptor activator of nuclear factor kappa-B ligand (RANKL) is important substance during osteoclastogenesis that resulted in alveolar bone loss of periodontitis. MicroRNAs (miRNAs) regulate gene expression in several biological processes including osteoclastogenesis. We investigated the function of microRNA-302a-3p (...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.26456
更新日期:2018-06-01 00:00:00
abstract::Long noncoding RNA (lncRNA) maternally expressed 3 (MEG3) has been implicated as a tumor suppressor gene in several human cancer types. However, little is known regarding its involvement and potential mechanism in human breast cancer. In this study, we explored the effect of MEG3 on the growth of human breast cancer c...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.27982
更新日期:2019-04-01 00:00:00
abstract::Four detergents have been compared for identification of the Plasmodium knowlesi variant antigen on infected erythrocytes by immunoprecipitation analysis. Erythrocytes infected with late trophozoite and schizont forms of cloned asexual parasites were labeled by lactoperoxidase-catalyzed radioiodination and extracted e...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.240240310
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:Long noncoding RNA (lncRNA) is emerging as a vital regulator in various cancers. Recently, it was found that lncRNA colorectal neoplasia differentially expressed (CRNDE) plays an oncogenic role, promoting cell proliferation and migration in hepatocellular carcinoma (HCC). However, the underlying regulatory m...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.28894
更新日期:2019-09-01 00:00:00
abstract::Macromolecules are sulfated during the vegetative growth of Dictyostelium discoideum. A characterisation of the structures of sulfated oligosaccharides associated with these macromolecules indicates that the oligosaccharides are heterogeneous. Endoglycosidase and pronase digestion were used with gel-filtration chromat...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.240380202
更新日期:1988-10-01 00:00:00
abstract::The in vitro growth of primary erythroleukemia cells has been examined in the presence and absence of the hormone erythropoietin (EPO). Although these leukemic cells had previously been considered to be hormone-independent, addition of EPO was found to be essential for maximum growth in culture. Erythroid colonies tha...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.240300404
更新日期:1986-01-01 00:00:00
abstract::X-ray atomic structure of recombinant Hell's gate globin I (HGbI) from Methylacidophilum infernorum was calculated from the X-ray diffraction data of two different types of crystals: obtained by classical hanging drop and by LB nanotemplate method under the same crystallization conditions. After the accurate compariso...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.24131
更新日期:2012-07-01 00:00:00
abstract::A new view of the cell nucleus is emerging based on the functional dynamics of nuclear architecture. The striking structural preservation of a variety of genomic processes on the nuclear matrix provides an important approach for correlating nuclear form and function. In situ labeling coupled with three-dimensional mic...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4644(1998)72:30/31+<238::AID-JC
更新日期:1998-01-01 00:00:00
abstract::Hepatitis B virus (HBV) is the most common of the hepatitis viruses that cause chronic liver infections in humans and it is considered a major global health problem. However, the mechanisms of HBV replication are complex and not yet fully understood. In this study, the HBV DNA-transfected HepG2.2.15 cell line and its ...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.24313
更新日期:2013-01-01 00:00:00
abstract::The cleavage of poliovirus precursor polypeptides occurs at specific amino acid pairs that are recognized by viral proteinases. Most of the polio-specific cleavages occur at glutamine-glycine (Q-G) pairs that are recognized by the viral-encoded proteinase 3C (formerly called P3-7c). In order to carry out a defined mol...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.240330105
更新日期:1987-01-01 00:00:00
abstract::Magnesium homeostasis in HL-60 promyelocytic leukemia cells was compared to that in neutrophyl-like HL-60 cells obtained by 1.3% DMSO treatment. Magnesium homeostasis was studied by the characterization of magnesium efflux, the identification of intracellular magnesium pools, and the regulation of intracellular ionize...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/(sici)1097-4644(19981201)71:3<441::aid-jcb
更新日期:1998-12-01 00:00:00
abstract::Cerebral ischemia/reperfusion (I/R) typically occurs after mechanical thrombectomy to treat ischemic stroke, generation of reactive oxygen species (ROS) after reperfusion may result in neuronal insult, ultimately leading to disability and death. Regulated in development and DNA damage responses 1 (REDD1) is a conserve...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.28737
更新日期:2019-09-01 00:00:00
abstract::Although effective for the treatment of hematological malignancies, the FDA approved proteasome inhibitors bortezomib and carfilzomib have limited efficacy in solid tumors including triple negative breast cancer (TNBC). Chemotherapy is the only option for treating TNBC due to the absence of specific therapeutic target...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.25783
更新日期:2017-05-01 00:00:00
abstract::The regulatory role of regucalcin on cell responses for tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor-beta1 (TGF-beta1) was investigated using the cloned normal rat kidney proximal tubular epithelial NRK52E cells overexpressing regucalcin. NRK52E cells (wild type) and stable regucalcin (RC)/pCX...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.21105
更新日期:2007-04-01 00:00:00
abstract::T-box (Tbx)3, a known transcriptional repressor, is a member of a family of transcription factors, which contain a highly homologous DNA binding domain known as the Tbx domain. Based on the knowledge that mutation of the Tbx3 gene results in limb malformation, Tbx3 regulates osteoblast proliferation and its expression...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.22035
更新日期:2009-02-15 00:00:00
abstract::Carotenoid cleavage dioxygenase (CCD) gene, ubiquitously found in numerous types of plants, are eminent in synthesizing the various volatile compounds (β-ionone, C13 -norisoprenoid, geranylacetone) known as apocarotenoids. These apocarotenoids have various biological functions such as volatile signals, allelopathic in...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.25919
更新日期:2017-09-01 00:00:00
abstract::The receptor for epidermal growth factor (EGF) is a glycosylated transmembrane phosphoprotein that exhibits EGF-stimulable protein tyrosine kinase activity. On EGF stimulation, the receptor undergoes a self-phosphorylation reaction at tyrosine residues located primarily in the extreme carboxyl-terminal region of the p...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.240290304
更新日期:1985-01-01 00:00:00
abstract::Multifidus muscle dysfunction is associated with the multifidus muscle injury (MMI), which ultimately result in the low-back pain. Increasing evidence shows that microRNAs (miRs) may be involved in multifidus muscle dysfunction. In this study, we tested the hypothesis that downregulation of let-7b-5p may inhibit the m...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.28020
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:The impact of aberrant expression of miRNAs, small noncoding RNAs of 19 to 23 nucleotide, has been reported in different types of cancer, such as breast cancer. Authors aim to investigate the role of circulating miRNA-335 as a diagnostic and prognostic marker for breast cancer. MATERIALS AND METHODS:miRNA-3...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.28168
更新日期:2019-06-01 00:00:00
abstract::P-selectin glycoprotein ligand-1 (PSGL-1) is the best-characterized selectin ligand that has been demonstrated to mediate leukocytes rolling on endothelium and leukocytes recruitment into inflamed tissue in vivo. In addition to its direct role in leukocyte capturing, PSGL-1 also functions as a signal-transducing recep...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.20213
更新日期:2005-02-01 00:00:00
abstract::High concentrations of nonesterified fatty acids (NEFAs) and β-hydroxybutyric acid (BHBA) induce lipid peroxidation, resulting in liver damage. Choline and methionine (Met) can promote energy balance and benefit liver health in transition dairy cows; however, the regulating mechanism remains unclear. In the present st...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.29494
更新日期:2019-11-03 00:00:00
abstract::Epigallocatechin-3-gallate (EGCG), the major green tea polyphenol, can reach the brain following oral intake and could thus act as an anti-tumoral agent targeting several key steps of brain cancer cells invasive activity. Because integrin-mediated extracellular matrix recognition is crucial during the cell adhesion pr...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.10667
更新日期:2003-11-01 00:00:00
abstract::Oxidative stress is an important underlying cause of many disease processes and may arise due to either increasing free radical generation or decreasing antioxidant defense systems. MicroRNAs (miRs) are 22-nucleotide non-coding RNAs that may regulate many intracellular processes; and, more recently, they have been imp...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.27475
更新日期:2018-08-30 00:00:00
abstract::In the present study, monoclonal antibodies were produced using porcine adipocyte extracts as the immunogen. Two of the monoclonal antibodies, designated CB6 and IB4, exhibited reactivity toward only cells containing lipid in stromal-vascular cell cultures. The antigens recognized by the CB6 and IB4 monoclonal antibod...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.240450311
更新日期:1991-03-01 00:00:00