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Bioactivity of melianone against Salmonella and in silico prediction of a membrane protein target

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Abstract

Melianone, the protolimonoid (24, 25-epoxyflindissone), was isolated from the medicinal tree species, Swietenia mahagoni (L.) JACQ (Meliaceae). The compound isolated from petroleum ether leaf extracts (5.39%) was quantified using high-performance thin-layer chromatography (HPTLC) method. In antimicrobial assays melianone inhibited Salmonella ser. Typhi with an MIC of 0.053 µM. Induced Fit Docking (IFD) of the ligand, melianone, with proteins involved in anaerobic virulence of the pathogen, revealed that it binds with FocA (a transport protein of formate ions) at its “periplasmic opening” with a glide energy of − 51.8576 kcal mol−1. Melianone altered the overall conformation of the protein (protomer A) by 0.347 Å RMSD. It induced a notable protein topology (Ω loop region) shift in the channel from an intermediate-open to a closed-state conformation and was supported by molecular dynamic simulations performed. FocA, a protein that contributes to its survival under anaerobic conditions, was further evaluated experimentally, after exposure of Salmonella ser. Typhi to melianone, resulting in the altered homeostasis of formate.

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Acknowledgements

A. Veni is thankful to the management of Sri Ramachandra Institute of Higher Education and Research (Deemed-to-be University) for the award of SRU-Chancellor fellowship for this study. Plants were authenticated by Prof (Retd.) P. Jayaraman, Director, Institute of Herbal Botany, Plant Anatomy Research Centre, West Tambaram, Chennai-45 (Reg. No of the certificate: PARC/2014/2059). We sincerely acknowledge the contributions of other reviewers for their constructive criticisms. We record with gratitudes the invaluable suggestions from Prof. V Ganesh, Dept. of Human Genetics (SRIHER, DU) towards improvement of this manuscript.

Funding

(Information that explains whether and by whom the research was supported). A. Veni is thankful to the management of Sri Ramachandra Institute of Higher Education and Research (Deemed-to-be University) for the award of SRU-Chancellor fellowship for this study.

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Authors and Affiliations

  1. Department of Biotechnology, Sri Ramachandra Institute of Higher Education and Research (Deemed To Be University), Porur, 600116, India

    A. Veni & T. S. Lokeswari

  2. Former Department of Medicinal Chemistry, Sri Ramachandra Institute of Higher Education and Research (Deemed To Be University), Porur, 600116, India

    G. N. Krishna Kumari

  3. Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, 600025, India

    D. Gayathri

  4. Department of Biotechnology, School of Bioscience and Technology, Vellore Institute of Technology (VIT) University, Vellore, 632014, India

    C. Sudandiradoss

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  1. A. Veni
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Correspondence to T. S. Lokeswari.

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Veni, A., Lokeswari, T.S., Krishna Kumari, G.N. et al. Bioactivity of melianone against Salmonella and in silico prediction of a membrane protein target. 3 Biotech 10, 460 (2020). https://doi.org/10.1007/s13205-020-02441-9

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