Synthesis, antimicrobial activity, and sustainable release of novel α-aminophosphonate derivatives loaded carrageenan cryogel

Int J Biol Macromol. 2020 Nov 15;163:96-107. doi: 10.1016/j.ijbiomac.2020.06.251. Epub 2020 Jun 29.


Novel α-aminophosphonates 4 were synthesized via one pot three-component reaction of 4-aminoantipyrine, aldehydes, triphenylphosphite and Lewis acid catalyst. The chemical structures of all the synthesized compounds were elucidated by IR, NMR and MS spectral analysis. The antimicrobial activity of 4 was tested in vitro against pathogenic microbes such as E.coli, S.aureus, A.niger and C.albicans. Three of them (4f-h) exhibited high antimicrobial activity and were loaded to carrageenan cryogel for drug delivery studies. With the aid of cellulose nanofibrils (CNF) as reinforcing material and glyoxal as a cross-linking agent, porous cryogels with improved mechanical properties were obtained. Among all, CAR-7 presents the optimum cryogel sample, which contained around 16% CNF and 0.2 mL/15 mL polymer blend. CAR-7 demonstrated highest mechanical compressive strength, porosity (80%), and swelling capacity (75%). Sustainable release behavior over 24 h was observed for the loaded cryogels. The antimicrobial activity of cryogels against S.aureus showed marginal differences between samples. CAR-9 (loaded with 4f) showed the highest reduction percentage in number of bacterial colonies (99.94%) followed by CAR-11 (loaded with 4h, 99.3%) and finally CAR-10 (loaded with 4g, 99.29%).

Keywords: Antimicrobial activity and sustainable release; Carrageenan; Cryogel.

MeSH terms

  • Aldehydes / chemistry
  • Ampyrone / chemistry
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Aspergillus niger / drug effects
  • Candida albicans / drug effects
  • Carrageenan / chemistry*
  • Cellulose / chemistry
  • Colony Count, Microbial
  • Compressive Strength
  • Cryogels / chemistry*
  • Delayed-Action Preparations
  • Drug Compounding / methods
  • Drug Liberation
  • Escherichia coli / drug effects
  • Glyoxal / chemistry
  • Microscopy, Electron, Scanning
  • Nanofibers / chemistry
  • Organophosphonates / chemical synthesis*
  • Organophosphonates / chemistry
  • Organophosphonates / pharmacology*
  • Porosity
  • Solubility
  • Staphylococcus aureus / drug effects


  • Aldehydes
  • Anti-Bacterial Agents
  • Cryogels
  • Delayed-Action Preparations
  • Organophosphonates
  • Ampyrone
  • Glyoxal
  • Carrageenan
  • Cellulose