2018
DOI: 10.1021/acs.jmedchem.8b01356
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Identification and Profiling of Hydantoins—A Novel Class of Potent Antimycobacterial DprE1 Inhibitors

Abstract: Tuberculosis is the leading cause of death worldwide from infectious diseases. With the development of drug-resistant strains of Mycobacterium tuberculosis, there is an acute need for new medicines with novel modes of action. Herein we are reporting the discovery and profiling of a novel hydantoin-based family of antimycobacterial inhibitors of the decaprenylphospho-beta-Dribofuranose 2-oxidase (DprE1). In this study we have prepared a library of more than a 100 compounds and evaluated them for their biologica… Show more

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Cited by 34 publications
(54 citation statements)
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“…Because there were no known synthetic methods for hydantoin-substituted enamides, we developed a new strategy based on oxime acylation (Scheme ). The readily available 5-arylidene-substituted hydantoin 1′ and p -methoxy derivative of 2-bromoacetophenone 2′ were used in a substitution reaction to obtain an intermediate ketone 3′ , which was subsequently converted to the corresponding oxime 4′ . The compound 4′ was then used in Fe-catalyzed acylation to obtain enamide 5′ ( Z / E = 61/39).…”
mentioning
confidence: 99%
“…Because there were no known synthetic methods for hydantoin-substituted enamides, we developed a new strategy based on oxime acylation (Scheme ). The readily available 5-arylidene-substituted hydantoin 1′ and p -methoxy derivative of 2-bromoacetophenone 2′ were used in a substitution reaction to obtain an intermediate ketone 3′ , which was subsequently converted to the corresponding oxime 4′ . The compound 4′ was then used in Fe-catalyzed acylation to obtain enamide 5′ ( Z / E = 61/39).…”
mentioning
confidence: 99%
“…The various steps involved are (1) ChemSketch 12 freeware was used to draw ninety-five structures, (2) Structure optimization of all the structures using MMFF94 force field existing in TINKER, (3) In the next step, Open3dAlign software was executed to align all the optimized structures, (4) Consensus pharmacophore modeling was completed using LIQUID plugin (installed on PyMOl 2.2) using the default settings [4][5][6].…”
Section: Structure Drawing Optimization and Alignmentmentioning
confidence: 99%
“…It is a vector borne neglected disease and recent reports suggest the emergence of resistance against existing drugs. The emergence of resistance is cause of high concern; therefore, developing novel therapeutics is an urgent need to eliminate this lethal disease [1][2][3]. Unfortunately, developing a new drug is a lengthy and expensive exercise; therefore, alternative methods like Computer Aided Drug Designing (CADD) must be used to derive a new therapeutic agent.…”
Section: Introduction Tuberculosis (Tb) Caused Bymentioning
confidence: 99%
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“…Spirocyclic skeletons are important synthetic targets due to their diversified biological activities and have been used as core components of various functional materials and ligands . With the rapid development of C–H bond functionalization, transition-metal-catalyzed annulation reactions have proven to be a powerful tool for obtaining various challenging but synthetically valuable spirocyclic molecules .…”
mentioning
confidence: 99%