Sulphamethazine derivatives as immunomodulating agents: New therapeutic strategies for inflammatory diseases

PLoS One. 2018 Dec 19;13(12):e0208933. doi: 10.1371/journal.pone.0208933. eCollection 2018.

Abstract

Sulfamethazine (SMZ) (1) is an antibacterial sulfa drug which suppresses the synthesis of dihydrofolic acid. It is used for the treatment of infections in livestock; such as gastrointestinal, and respiratory tract infections. During the current study, synthesis, characterization, and evaluation of immunomodulatory activities of derivatives of sulfamethazine (SMZ) (3-39) was carried out. These derivatives were synthesized by the reaction of sulfamethazine with a range of acid chlorides. All the compounds were characterized by using modern spectroscopic techniques, such as 1H-, and 13C-NMR, EI-MS, and HRFAB-MS. Compounds 3-10, 14, and 15 were identified as new compounds. Immunomodulatory effect of compounds 3-39 on different parameters of innate immune response was evaluated, including the production of Reactive Oxygen Species (ROS) from human whole blood and isolated polymorphonuclear neutrophils (PMNs), nitric oxide (NO), and pro-inflammatory cytokine TNF-α. All the new compounds, except 14 and 15, showed a significant anti-inflammatory activity. Compounds 3-39 were also evaluated for their anti-bacterial activity and cytotoxicity (3T3 mouse fibroblast cell lines). All the compounds were found to be non-cytotoxic against normal cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Folic Acid / analogs & derivatives
  • Folic Acid / biosynthesis
  • Humans
  • Immunity, Innate / drug effects*
  • Immunologic Factors / chemical synthesis
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology*
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Mice
  • Neutrophils / chemistry
  • Neutrophils / drug effects
  • Nitric Oxide / chemistry
  • Reactive Oxygen Species / chemistry
  • Structure-Activity Relationship
  • Sulfamethazine / analogs & derivatives
  • Sulfamethazine / chemistry
  • Sulfamethazine / pharmacology*
  • Sulfamethizole / chemical synthesis
  • Sulfamethizole / chemistry
  • Sulfamethizole / pharmacology

Substances

  • Immunologic Factors
  • Reactive Oxygen Species
  • Sulfamethizole
  • Nitric Oxide
  • dihydrofolate
  • Sulfamethazine
  • Folic Acid

Grant support

HMH is thankful to the ICCBS for the post-doctoral fellowship for one year. HMH is also thankful to the COMSATS (The Commission on Science and Technology for Sustainable Development in the South) for the travel support.