Bis-spirochromanones as potent inhibitors of Mycobacterium tuberculosis: synthesis and biological evaluation

On the basis of reported antimycobacterial property of chroman-4-one pharmacophore, a series of chemically modified bis-spirochromanones were synthesized starting from 2-hydroxyacetophenone and 1,4-dioxaspiro[4.5] decan-8-one using a Kabbe condensation approach. The synthesized bis-spirochromanones...

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Bibliographic Details
Published in:Molecular diversity 2017-11, Vol.21 (4), p.999-1010
Main Authors: Dongamanti, Ashok, Aamate, Vikas Kumar, Devulapally, Mohan Gandhi, Gundu, Srinivas, Balabadra, Saikrishna, Manga, Vijjulatha, Yogeeswari, Perumal, Sriram, Dharmarajan, Balasubramanian, Sridhar
Format: Article
Language:English
Subjects:
Antitubercular Agents - chemical synthesis
Antitubercular Agents - metabolism
Antitubercular Agents - pharmacology
Antitubercular Agents - toxicity
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Biochemistry
Biological activity
Biomedical and Life Sciences
Chemical synthesis
Chemistry Techniques, Synthetic
Chromans - chemical synthesis
Chromans - metabolism
Chromans - pharmacology
Chromans - toxicity
Crystal structure
HEK293 Cells
Humans
Life Sciences
Microbial Sensitivity Tests
Molecular Docking Simulation
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - metabolism
Organic Chemistry
Original Article
Pharmacy
Polymer Sciences
Protein Conformation
Spiro Compounds - chemistry
Structure-Activity Relationship
Toxicity
Tuberculosis
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Summary:On the basis of reported antimycobacterial property of chroman-4-one pharmacophore, a series of chemically modified bis-spirochromanones were synthesized starting from 2-hydroxyacetophenone and 1,4-dioxaspiro[4.5] decan-8-one using a Kabbe condensation approach. The synthesized bis-spirochromanones were established based on their spectral data and X-ray crystal structure of 6e . All synthesized compounds were evaluated against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain, finding that some products exhibited good antimycobacterial activity with minimum inhibitory concentration as low as 3.125 μ g/mL . Docking studies were carried out to identify the binding interactions of compounds II , 6a and 6n with FtsZ. Compounds exhibiting good in vitro potency in the MTB MIC assay were further evaluated for toxicity using the HEK cell line. Graphical Abstract
ISSN:1381-1991
1573-501X
DOI:10.1007/s11030-017-9779-y