2. Academic Validation
  3. Repurposing of a drug scaffold: Identification of novel sila analogues of rimonabant as potent antitubercular agents

Repurposing of a drug scaffold: Identification of novel sila analogues of rimonabant as potent antitubercular agents

  • Eur J Med Chem. 2016 Oct 21:122:723-730. doi: 10.1016/j.ejmech.2016.07.009.
Remya Ramesh 1,  Rahul D Shingare 1,  Vinod Kumar 2,  Amitesh Anand 3,  Swetha B 4,  Sridhar Veeraraghavan 5,  Srikant Viswanadha 5,  Ramesh Ummanni 6,  Rajesh Gokhale 3,  D Srinivasa Reddy 7
Affiliations

Affiliations

  • 1 CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110 025, India.
  • 2 CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008, India.
  • 3 CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110025, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110 025, India.
  • 4 CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
  • 5 Incozen Therapeutics Pvt. Ltd., Alexandria Knowledge Park, Turkapally, Rangareddy, 500078, India.
  • 6 CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110 025, India.
  • 7 CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110 025, India. Electronic address: ds.reddy@ncl.res.in.
PMID: 27476117 DOI: 10.1016/j.ejmech.2016.07.009
Abstract

The structural similarity between an MmpL3 inhibitor BM212, and a Cannabinoid Receptor modulator rimonabant, prompted us to investigate the anti-tubercular activity of rimonabant and its analogues. Further optimization, particularly through incorporation of silicon into the scaffold, resulted in new compounds with significant improvement in anti-tubercular activity against Mycobacterium tuberculosis (H37Rv). The sila analogue 18a was found to be the most potent antimycobacterial compound (MIC, 31 ng/mL) from this series with an excellent selectivity index.

Keywords

BM212; Drug repurposing; MmpL3 inhibitor; Rimonabant; Sila analogue; Tuberculosis.

Figures