Current Issue : July - September Volume : 2017 Issue Number : 3 Articles : 5 Articles
The �²3 adrenergic receptor is raising as an important drug target for the treatment of\npathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several\nattempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron\nis the only available drug on the market that targets this receptor approved for the treatment of\noveractive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA\n(Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially\nlife-threatening side effects associated with the administration of Mirabegron, casting doubts on the\ncontinuity of this compound. Therefore, it is of utmost importance to gather information for the\nrational design and synthesis of new �²3 adrenergic ligands. Herein, we present the first combined\n2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA\n(three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity\nIndex Analysis) study on a series of potent �²3 adrenergic agonists of indole-alkylamine structure.\nWe found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor,\nlipophilicity and molar refractivity properties of the compounds to generate new promising molecules.\nFinally, based on our analysis, a summary and a regiospecific description of the requirements for\nimproving �²3 adrenergic activity is given....
Alzheimer’s disease (AD) progresses due to beta amyloid aggregation and decreased acetylcholine level. Amyloid-β peptide (Aβ) formed by the continuous proteolytic processing of β-amyloid precursor protein (β APP) by β-secretase (BACE1) and γ-secretase (BACE2), plays a vital role in the pathogenesis of Alzheimer’s disease (AD). Evaluated dipeptides and heterocyclic fused dipeptide derivative exhibit inhibitory action against acetyl cholinesterase enzyme. In-silico docking analysis for dipeptides and heterocyclic fused dipeptide was carried out using GLIDE software. The docking score of DP IV and DPI was found to be -7.63 and -7.08 and the standard donepezil (AChE inhibitor) showed docking score of -4.97 using GLIDE against AChE. In-vitro enzyme inhibition assay was carried out for AChE enzyme and the IC50 value of DP IV was found to be 0.399 μg/ml and the standard donepezil (AChE inhibitor) was found to be 0.065 μg/ml. Based on the results obtained from in-silico docking studies and in-vitro enzyme inhibition, both are correlated with each other....
Cuminum cyminum (family Apiaceae) is used as an ingredient in many home remedies and ayurvedic preparations. The strong aroma of cumin seeds is due to the presence of compound cuminaldehyde or 4-isopropylbenzaldehyde. Cuminaldehyde is also the constituent of several essential oils of eucalyptus, myrrh, cassia, cumin and many other plants. From the literature, it was observed that no such evidence of cuminaldehyde, a prime constituent of numerous essential oil containing plants as an anti-inflammatory agent has been indicated against any specified target. By utilizing in-silico approach using docking technique(s), the binding sites of the ligand were explored. The role of cuminaldehyde and its bioconverted ligands as anti-inflammatory agent were investigated by in-silico molecular docking method utilizing lipoxygenase (LOX) and cyclooxygenase-2 (COX-2) as the target. The bioconverted molecules were 10 predicted molecules, which were predicted by the server based on the degradation of cuminaldehyde by both aerobic and anaerobic biotransformation applying specifically designed algorithms. The study revealed the role of cuminaldehyde as the potential candidate for preventing inflammation, based on the Dock Score. It was also found that the bioconverted compounds, probably formed by the degradation of cuminaldehyde by microbes, demonstrated more potent activity than the parent compound. Analogs 3, 6, 8, 10 and 11 displayed remarkably high binding affinity with both the inflammatory targets; LOX and COX. Except compound 9, all the other molecules exhibited significant COX-2 inhibition. Thus, the study revealed the ability of cuminaldehyde and its predicted bioactivated components as an anti-inflammatory candidate....
Over the past years natural products and/or their derivatives have continued\nto provide cancer chemotherapeutics. Glycosides derivatives of emodin are\nknown to possess anticancer activities. An in silico study was carried out to\nevaluate emodin derivatives as inhibitors of Arylamine N-Acetyltransferase 2,\nCyclooxygenase 2 and Topoisomerase 1 enzymes, predict their pharmacokinetics\nand explore their bonding modes. Molecular docking study suggested\nthat D2, D5, D6 and D9 to be potent inhibitors of NAT2, while D8 was suggested\nto be a potent inhibitor of TOP1. Derivatives D2, D5, D6 and D9 bind\nto the same pocket with different binding conformation. Pharmacokinetic\nstudy suggested that selected emodin derivatives can be potential cancer chemotherapeutic\nagent. Physicochemical parameters such density, balaban index,\nsurface tension, logP and molar reflectance correlated to compounds activity.\nThese finding provides a potential strategy towards developing NAT2\nand TOP1 inhibitors....
The growing number of studies on G protein-coupled receptors (GPCRs) family are a\nsource of noticeable improvement in our understanding of the functioning of these proteins. GPCRs\nare responsible for a vast part of signaling in vertebrates and, as such, invariably remain in the\nspotlight of medicinal chemistry. A deeper insight into the underlying mechanisms of interesting\nphenomena observed in GPCRs, such as biased signaling or allosteric modulation, can be gained\nwith experimental and computational studies. The latter play an important role in this process, since\nthey allow for observations on scales inaccessible for most other methods. One of the key steps in\nsuch studies is proper computational reconstruction of actual ligand-receptor or protein-protein\ninteractions, a process called molecular docking. A number of improvements and innovative\napplications of this method were documented recently. In this review, we focus particularly on\ninnovations in docking to GPCRs....
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