24 research outputs found
Methyl 3-[(1,1-dioxo-1λ6,2-benzothiazol-3-yl)amino]-5-nitrothiophene-2-carboxylate
The title nitrothiophene compound, C13H9N3O6S2, crystallizes with two independent molecules in the asymmetric unit; the molecular structure of each is stabilized by an intramolecular N—H...O hydrogen bond. The two molecules adopt flattened but slightly different conformations, viz. the dihedral angle between the thiophene ring and the essentailly planar 1,2-benzisothiazole fragment (r.m.s. deviations = 0.0227 and 0.0108 Å, respectively) is 15.62 (11)° in one molecule and 5.46 (11)° in the other. In the crystal, molecules are arranged into layers parallel to (-111) with weak Car—H...O interactions formed within the layer. N—H...O hydrogen bonds also occur. There are π–π stacking interactions between the molecules in neighbouring layers, the distance between the centroids of the 1,2-benzisothiazole benzene rings being 3.8660 (16) Å. Moreover, dipolar S=O...C=O interactions with an O...C distance of 2.893 (3) Å are observed between the symmetry-independent molecules in different layers. The title compound showed weak inhibition of HLE (human leukocyte elastase)
Chemically Diverse Compound Library
24-27Open Source Drug Discovery
(OSDD) foresees building of a chemically diverse compound library which could
greatly aid the project’s drug discovery process.
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Strategies towards the synthesis of anti-tuberculosis drugs
International audienc
A Chemical Genetic Approach for Covalent Inhibition of Analogue-Sensitive Aurora Kinase
The perturbation of protein kinases with small organic
molecules
is a powerful approach to dissect kinase function in complex biological
systems. Covalent kinase inhibitors that target thiols in the ATP
binding pocket of the kinase domain proved to be ideal reagents for
the investigation of highly dynamic cellular processes. However, due
to the covalent inhibitors' possible off-target reactivities, it is
required that the overall shape of the inhibitor as well as the intrinsic
reactivity of the electrophile are precisely tuned to favor the reaction
with only the desired cysteine. Here we report on the design and biological
characterization of covalent anilinoquinazolines as potent inhibitors
of genetically engineered Aurora kinase in fission yeast
Identification of New Molecular Entities (NMEs) as Potential Leads against Tuberculosis from Open Source Compound Repository.
The purpose of this study was to provide a number of diverse and promising early-lead compounds that will feed into the drug discovery pipeline for developing new antitubercular agents. The results from the phenotypic screening of the open-source compound library against Mycobacterium smegmatis and Mycobacterium bovis (BCG) with hit validation against M. tuberculosis (H37Rv) have identified novel potent hit compounds. To determine their druglikeness, a systematic analysis of physicochemical properties of the hit compounds has been performed using cheminformatics tools. The hit molecules were analysed by clustering based on their chemical finger prints and structural similarity determining their chemical diversity. The hit compound library is also filtered for druglikeness based on the physicochemical descriptors following Lipinski filters. The robust filtration of hits followed by secondary screening against BCG, H37Rv and cytotoxicity evaluation has identified 12 compounds with potential against H37Rv (MIC range 0.4 to 12.5 μM). Furthermore in cytotoxicity assays, 12 compounds displayed low cytotoxicity against liver and lung cells providing high therapeutic index > 50. To avoid any variations in activity due to the route of chemical synthesis, the hit compounds were re synthesized independently and confirmed for their potential against H37Rv. Taken together, the hits reported here provides copious potential starting points for generation of new leads eventually adds to drug discovery pipeline against tuberculosis