Tween 20-/H₂O Promoted Green Synthesis, Computational and Antibacterial Activity of Amino Acid Substituted Methylene Bisphosphonates

GRAPHICAL ABSTRACT

Abstract

A green synthesis of amino acid-substituted methylene bisphosphonates (4a-j) is achieved via a one-pot, three-component reaction of dialkylphosphite, triethyl orthoformate, and various amino acids catalyzed by Tween 20 in aqueous medium. The synthesized compounds were characterized by infrared spectroscopy, nuclear magnetic resonance (¹H, ¹³C, and ³¹P), mass spectra, and elemental analysis. These were screened for in vitro antibacterial activity against clinically isolated bacteria Klebsiella pneumonia, Pseudomonas aeruginosa (Gram –ve), and Staphylococcus aureus, Bacillus subtilis (Gram +ve). Among all the compounds, 4a and 4d showed higher activity against all bacterial strains compared with standard ciprofloxacin. To further support the work, molecular docking studies against the bacterial target enzyme, Type IIA topoisomerase revealed that some of the lead molecules 4j (–7.4 kcal/mol), 4e (–7.1 kcal/mol), 4a (–6.8 kcal/mol), and 4d (–6.8 kcal/mol) showed good protein–ligand interactions.

Keywords::

• Bisphosphonates
• Tween 20
• docking
• antibacterial activity

ACKNOWLEDGMENTS

We thank Prof. C.D. Reddy, Department of Chemistry, S.V. University, Tirupati, for his helpful discussions.