Alzheimer's disease (AD) is one of the most significant neurodegenerative disorders and its symptoms mostly appear in aged people. Catechol-o-methyltransferase (COMT) is one of the known target enzymes responsible for AD. With the use of 23 known inhibitors of COMT, a query has been generated and validated by screening against the database of 1500 decoys to obtain the GH score and enrichment value. The crucial features of the known inhibitors were evaluated by the online ZINC Pharmer to identify new leads from a ZINC database. Five hundred hits were retrieved from ZINC Pharmer and by ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering by using FAF-Drug-3 and 36 molecules were considered for molecular docking. From the COMT inhibitors, opicapone, fenoldopam, and quercetin were selected, while ZINC63625100_413 ZINC39411941_412, ZINC63234426_254, ZINC63637968_451, and ZINC64019452_303 were chosen for the molecular dynamics simulation analysis having high binding affinity and structural recognition. This study identified the potential COMT inhibitors through pharmacophore-based inhibitor screening leading to a more complete understanding of molecular-level interactions.

BackgroundTuberculosis (TB) is the second leading cause of death from a single infectious organism, demanding attention towards discovery of novel anti-tubercular compounds. Natural products or their derivatives have provided more than 50% of all existing drugs, offering a chemically diverse space for discovery of novel drugs.DescriptionBioPhytMol has been designed to systematically curate and analyze the anti-mycobacterial natural product chemical space. BioPhytMol is developed as a drug-discovery community resource with anti-mycobacterial phytomolecules and plant extracts. Currently, it holds 2582 entries including 188 plant families (692 genera and 808 species) from global flora, manually curated from literature. In total, there are 633 phytomolecules (with structures) curated against 25 target mycobacteria. Multiple analysis approaches have been used to prioritize the library for drug-like compounds, for both whole cell screening and target-based approaches. In order to represent the multidimensional data on chemical diversity, physiochemical properties and biological activity data of the compound library, novel approaches such as the use of circular graphs have been employed.ConclusionBioPhytMol has been designed to systematically represent and search for anti-mycobacterial phytochemical information. Extensive compound analyses can also be performed through web-application for prioritizing drug-like compounds. The resource is freely available online at http://ab-openlab.csir.res.in/biophytmol/.Graphical AbstractBioPhytMol: a drug discovery community resource on anti-mycobacterial phytomolecules and plant extracts generated using Crowdsourcing. The platform comprises of manually curated data on antimycobacterial natural products along with tools to perform structure similarity and visualization. The platform allows for prioritization of drug like natural products for antimycobacterial drug discovery.Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-014-0046-2) contains supplementary material, which is available to authorized users.

In the current investigation, we prepared a series of novel spiro[indole-thiazolidines] derivatives (5a-5h) from 5-substituted isatin derivatives and thioglycolic acid (TGA) with ZrSiO as an efficient catalyst under microwave irradiation. The significant merits of this protocol have some significant merits such as simplicity in operation, simple, efficient workup, good practical yields of product and the employment of recyclable catalyst. All the new synthesized scaffold has been well characterized by various spectroscopic methods and elemental analysis. All the spiro scaffolds were subjected to in vitro anti-mycobacterial activity against the Mycobacterium tuberculosis (HRv) strain. We have carried out molecular docking study of our synthesized compounds. We also calculated theoretically ADME-Tox parameters for synthesized compounds.

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