Synthesis, antibacterial activity study, molecular docking and molecular properties prediction of new organo phosphonate derivatives

Abstract

A series of organophosphorous compounds (3a - 3m) containning phosphonate functional group have been synthesized efficiently with high speed and good yield. All the compounds were correctly characterized using different spectroscopic techniques (IR, Mass, 1H, 13C and 31P-NMR). These compounds were screened for their antibacterial activity. All the synthesized derivatives showed good antibacterial activities. 3g compound showed the best activity against one Gram-positive (Staphylococas aureus) and two Gramnegative (Escherichia coli and Klebsiella pneumoniae) species. In order to predict binding interaction between active site of bacterial enzyme and 3g, molecular docking was performed, into the crystal structures of DNA-gyrase cleavage complex of S. aureus (Gram+ve) with PDB_ID:5CDQ and the cleavage complex of topoisomerase Top. IV of K. pneumoniae (Gram-ve) with PDB_ID:5EIX using autodock/vina, an open source software. The molecule showed strong interaction due to H bonding, pi- pi interaction and hydrophobic interaction with active site amino acids. The synthesized compounds were also submitted to drug likeness model programs e.g molinspiration and osiris to predict bioavailability and toxicity profiles which are important for selection of the best drug candidate among all synthesized compounds. With these results we conclusively demonstrated the selected structural analogues can act as potential antibacterial agents.