Synthesis and in vitro evaluation of antimycobacterial and cytotoxic activity of new α,β-unsaturated amide, oxazoline and oxazole derivatives from l-serine

Bioorg Med Chem Lett. 2020 May 1;30(9):127074. doi: 10.1016/j.bmcl.2020.127074. Epub 2020 Mar 2.

Abstract

The synthesis of 19 compounds derived from l-serine and analogs of p-substituted cinnamic acid is reported. Oxazolines 9 and oxazoles 10 have high antitubercular activity with Minimum Inhibitory Concentration (MIC) of 0.7812-25.0 µg/mL (3.21-100.3 µM), against two strains of Mycobacterium tuberculosis sensitive to first-line drugs Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB), Pyrazinamide (PZE) (H37Rv) and a clinical isolate resistant to INH, RIF and EMB (G122). The cytotoxic evaluation shows that oxazoles have low activity, finding viability>96% against the VERO cell line. The results show these compounds could be considered as future alternatives for antitubercular treatment.

Keywords: Acrylamides; Antitubercular activity; Cytotoxicity; Oxazoles; Oxazolines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Drug Resistance, Multiple, Bacterial
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects
  • Serine / analogs & derivatives*
  • Serine / chemical synthesis
  • Serine / chemistry
  • Serine / pharmacology*
  • Vero Cells

Substances

  • Antineoplastic Agents
  • Antitubercular Agents
  • Serine