1,3-Oxazine-2-one derived dual-targeted molecules against replicating and non-replicating forms of Mycobacterium tuberculosis.

Authors :: Velappan AB
Kesamsetty D
Datta D
Ma R
Hari N
Franzblau SG
Debnath J
Source :: European journal of medicinal chemistry [Eur J Med Chem] 2020 Dec 15; Vol. 208, pp. 112835. Date of Electronic Publication: 2020 Sep 13.
Publication Year :: 2020
Abstract: The high mortality rate and increasing prevalence of resistant Mtb are the major concerns for the Tuberculosis (TB) treatment in this century. To curtail the prevalence of resistant Mtb, we have prepared 1,3-oxazine-2-one based dual targeted molecules. Compound 67 and 68 were found to be equally active against replicating and non-replicatiing form of Mtb (MIC <subscript>MABA</subscript> 3.48 and 2.97 μg/ml; MIC <subscript>LORA</subscript> 2.94 and 2.15 μg/ml respectively). They had found to suppress the biosynthesis of alfa, methoxy and keto-mycolate completely, as well as inhibit enzymatic activity of MenG (IC <subscript>50</subscript>  = 9.11 and 6.25 μg/ml respectively for H37Ra; IC <subscript>50</subscript>  = 11.76 and 10.88 μg/ml respectively for M smegmatis).<br />Competing Interests: Declaration of competing interest There is no conflict of interest with others.<br /> (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Subjects :: Antitubercular Agents chemical synthesis
Antitubercular Agents toxicity
Bacterial Proteins antagonists & inhibitors
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors pharmacology
Enzyme Inhibitors toxicity
Leukocytes, Mononuclear drug effects
Methyltransferases antagonists & inhibitors
Microbial Sensitivity Tests
Molecular Structure
Mycobacterium smegmatis drug effects
Mycolic Acids metabolism
Oxazines chemical synthesis
Oxazines toxicity
Structure-Activity Relationship
Antitubercular Agents pharmacology
Mycobacterium tuberculosis drug effects
Oxazines pharmacology

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