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

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Abstract

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 \(3.125\, \upmu \hbox {g/mL}\). 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.

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Acknowledgements

The authors thank The Head, Department of Chemistry, Osmania University, Hyderabad, for providing laboratory facilities. A.V.K. thanks CSIR for Ph.D. fellowship. B.S.K. thanks Schrödinger Suite 2011, Glide5.6 software, LLC. We thank CFRD analytical team for providing spectral analysis facilities.

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Authors and Affiliations

  1. Green and Medicinal Chemistry Lab, Department of Chemistry, Osmania University, Hyderabad, Telangana State, 500 007, India

    Ashok Dongamanti, Vikas Kumar Aamate, Mohan Gandhi Devulapally & Srinivas Gundu

  2. Molecular Modeling and Medicinal Chemistry group, Department of Chemistry, Osmania University, Hyderabad, Telangana State, 500 007, India

    Saikrishna Balabadra & Vijjulatha Manga

  3. Department of Pharmacy, Birla Institute of Technology and Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, Telangana State, 500 078, India

    Perumal Yogeeswari & Dharmarajan Sriram

  4. X-ray Crystallography Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana State, 500 007, India

    Sridhar Balasubramanian

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  1. Ashok Dongamanti
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Correspondence to Ashok Dongamanti.

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Dongamanti, A., Aamate, V.K., Devulapally, M.G. et al. Bis-spirochromanones as potent inhibitors of Mycobacterium tuberculosis: synthesis and biological evaluation. Mol Divers 21, 999–1010 (2017). https://doi.org/10.1007/s11030-017-9779-y

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