Synthesis, X-ray crystallographic study and molecular docking of new α-sulfamidophosphonates: POM analyses of their cytotoxic activity

Abstract A series of novel α-sulfamidophosphonate derivatives was rationally designed and synthesized following the principle of the superposition of bioactive substructures by the combination of sulfonamide, aldehyde and triethylphosphite. The relative cytotoxicity of these derivatives in comparison to chlorambucil has been reported. The crystal structure of diethyl phenyl (N-phenylsulfamoylamino)methylphosphonate has been determined. This crystal belongs to the C 2/c space group. The P atom has a distorted tetrahedral configuration with the O–P–O angle as the minimum bond angle (105.34) and one of the O P–O angles as the maximum angle (116.18). In addition, the results of bioinformatics POM (Petra, Osiris, Molinspiration) analyses and molecular docking show that all compounds exhibited good bioavailability, pharmacokinetic, and no toxicity profiles. Furthermore, drug likeness analysis suggests that the synthesized α-sulfamidophosphonate derivatives might have appropriate oral absorption and brain penetration for therapeutic applications. As the compounds were found to be non-toxic and in a safe range containing an important antiviral O,O-pharmacophore site, they present good candidates for further antiviral study.