2. Academic Validation
  3. Transferrin conjugates of antitubercular drug isoniazid: Synthesis and in vitro efficacy

Transferrin conjugates of antitubercular drug isoniazid: Synthesis and in vitro efficacy

  • Eur J Med Chem. 2019 Dec 1:183:111713. doi: 10.1016/j.ejmech.2019.111713.
Yogesh B Sutar 1,  Jaishree K Mali 1,  Vikas N Telvekar 2,  Raju S Rajmani 3,  Amit Singh 3
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, 400 019, India.
  • 2 Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, 400 019, India. Electronic address: vn.telvekar@ictmumbai.edu.in.
  • 3 Department of Microbiology and Cell Biology (MCBL), Centre for Infectious Disease Research (CIDR), Indian Institute of Science (IISc), Bangalore, 560 012, India.
PMID: 31557610 DOI: 10.1016/j.ejmech.2019.111713
Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become the world's leading killer disease due to a single infectious agent which survives in the host macrophage for the indefinite period. Hence, it is necessary to enhance the efficacy of the clinically existing antitubercular agents or to discover new anti antitubercular agents. Here, we report the synthesis, characterization and antimycobacterial evaluation of protein-drug conjugates. A carrier protein, Transferrin (Tf) was covalently conjugated to isoniazid (INH) utilizing hydrazone and amide linkers. The purity of the reactions was confirmed by SDS-PAGE while conjugation was confirmed by UV-visible spectrophotometry, MALDI-TOF analysis, and FTIR spectrophotometry. The in vitro antitubercular assay result showed that the inhibitory activity of the parent drug was conserved in both the conjugates. The conjugates were effective against intracellular Mtb H37Rv and were devoid of cytotoxic effect at therapeutic concentration.

Keywords

Conjugates; H37Rv; Isoniazid; Mycobacterium tuberculosis; Transferrin.

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