Synthesis of novel alkylphosphonates as promising antimicrobial drugs: Computational molecular docking studies

Abstract

For the first time, a series of alkylphosphonate derivatives were synthesized from diethyl ((2-chloroethoxy)methyl)phosphonate (1) to give the intermediate diethyl ((2-iodoethoxy)methyl)phosphonate (2) in good to excellent yields (85–94%) by a two-step process and evaluated against different bacterial strains and fungal strains. Compounds diethyl (2-(benzothiazol-2-ylamino)ethoxy)methylphosphonate (4a), diethyl (2-(4-chlorobenzothiazol-2-ylamino)ethoxy)methylphosphonate (4 b), diethyl (2-(1H-indazol-6-ylamino)ethoxy)methylphosphonate (4c), diethyl(2-((2-(3,4-dihydroxyphenyl)-2-hydroxyethyl)(methyl)amino)ethoxy)methylphosphonate (4e) and diethyl (2-(4-(N-pyrimidin-2-ylsulfamoyl)phenylamino)ethoxy)methylphosphonate (4i) unveiled remarkable anti-bacterial activity against S. aureus, B. subtilis, P. aeruginosa and K. pneumoniae and anti-fungal activity against A. niger and P. chrysogenum when compared with the standard drugs streptomycin and ketoconazole at 12.5, 25, 50 and 100 µg/mL concentrations. In silico molecular docking studies gave an insight about binding interactions and performed for all the synthesized compounds. Results disclosed that all the designed compounds shown moderate to high docking scores between −6.2 to −8.9 K. cal/mol against DNA gyrase protein using streptomycin (–6.8) as a standard drug. Specifically, 4a, 4 b, 4c, 4e and 4i displayed significant binding affinity with highest docking scores which emerged as potential lead compounds.

Graphical Abstract

Keywords:

• Alkylphosphonates
• anti-bacterial activity
• anti-fungal activity
• molecular docking

Disclosure statement

There is no conflict of interest disclosed by authors.