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Discovery of Rimonabant and its potential analogues as anti-TB drug candidates

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Abstract

Rimonabant and its analogues have been synthesized in moderate to good yields using a simple synthetic route. All the newly synthesized compounds were subjected to in vitro screening against M. tuberculosis and M. smegmatis. The most potent analogue JMG-14 exhibits MIC value of 3.13 compared to 3.25 and 50 µg/ml for ethambutol and pyrazinamide, respectively. The molecular docking reveals that pyrazole ring, number and position of halogen atoms play a crucial role in deciding interactions with MTCYP-121. These findings open up a new avenue in the search of potent anti-TB drugs with rimonabant and its novel analogue JMG-14 as lead molecules.

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Acknowledgments

JMG gratefully acknowledges CSIR-OSDD, CSIR-ORIGIN and DST-SERB, for the financial support.

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Authors and Affiliations

  1. Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune, 411008, India

    J. M. Gajbhiye, N. A. More & Manoj D. Patil

  2. Centre for Chemical Biology, Indian Institute of Chemical Technology, Hyderabad, 500607, India

    R. Ummanni & S. S. Kotapalli

  3. Tuberculosis Drug Discovery Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Hyderabad, 500078, India

    P. Yogeeswari & D. Sriram

  4. Department of Chemistry, VidyaBharati College, Camp, Amravati, 444602, India

    V. H. Masand

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  1. J. M. Gajbhiye
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  2. N. A. More
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  3. Manoj D. Patil
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  4. R. Ummanni
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  5. S. S. Kotapalli
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  7. D. Sriram
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  8. V. H. Masand
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Correspondence to J. M. Gajbhiye.

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Gajbhiye, J.M., More, N.A., Patil, M.D. et al. Discovery of Rimonabant and its potential analogues as anti-TB drug candidates. Med Chem Res 24, 2960–2971 (2015). https://doi.org/10.1007/s00044-015-1346-4

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  • DOI: https://doi.org/10.1007/s00044-015-1346-4

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