Synthesis and potent antimicrobial activity of novel coumarylthiazole α-aminophosphonates derivatives

Mol Divers. 2022 Apr;26(2):1161-1174. doi: 10.1007/s11030-021-10242-2. Epub 2021 Jun 12.

Abstract

Herein, we reported a novel series of α-aminophosphonates derivatives (IV)a-m bearing an important pharmacophore coumarylthiazole moiety. All the new compounds have been synthesized via Kabachnik-Fields reaction under ultrasonic irradiation. The products were obtained in good yield with a simple workup and were confirmed using various spectroscopic methods. All these compounds (IV)a-m were screened for their in vitro for antimicrobial activity against thirteen Gram-negative bacteria and five Gram-positive bacteria and Candida albicans strains. The results showed that all the synthesized compounds exhibited moderate antibacterial activities against both references and multidrug-resistant and antifungal strains. The compound (IV)e showed the highest activities against all pathogens of the tested microbial strains with MIC of 0.125 μg/mL. The compounds (IV)h, (IV)f, (IV)b, and (IV)d exhibited moderate and promising activities with MIC of 0.125 μg/mL. Structure-activity relationship revealed that inhibitory activity of the synthesized compounds is related to the type of the substituted group on phenyl rings, and these results showed that the electron-donating groups at ortho and para positions have a high relationship increasing antimicrobial activities than the electron-withdrawing groups. These results confirm that coumarylthiazole α-aminophosphonates compounds can be potential antimicrobial drugs candidate.

Keywords: Antimicrobial; Coumarylthiazole; Kabachnik–Fields reaction; Multidrug-resistant; α-aminophosphonates.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Infective Agents* / chemistry
  • Antifungal Agents
  • Gram-Negative Bacteria
  • Gram-Positive Bacteria
  • Microbial Sensitivity Tests
  • Organophosphonates* / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Antifungal Agents
  • Organophosphonates