Green synthesis, antibacterial, antiviral and molecular docking studies of α-aminophosphonates

Abstract An efficient method for the synthesis of α-aminophosphonate derivatives has been developed with different functional groups under catalyst and solvent free conditions at room temperature in both conventional and ultrasonication methods. Ultrasonication method offers excellent yields within shorter reaction times. All the title compounds 4a–l were tested for their antibacterial, antiviral activity using Gram-positive bacteria (Staphylococcus aureus, and Bacillus subtilis), Gram-negative bacteria (Klebsiella pneumoniae and Escherichia coli) and NDV infected embryonated eggs (in ovo) and NDV infected BHK-21 cell lines (in vitro) respectively. Besides, molecular docking studies were also carried out to the title compounds against Hemagglutinin-neuramidase enzyme to determine the therapeutic binding efficacy of the ligands synthesized. The results indicated that, among the title compounds, compounds such as 4f, 4l, 4k, 4b, 4i and 4h have shown high content of antibacterial and antiviral activity than the rest of the compounds and the level activity was high when compared to the standard, ribavirin. Based on the results, it is concluded that, the reported α-aminophosphonates will open new vistas and stands as a new generation of antiviral and antibacterial drug candidates in future. Graphical Abstract

[1]  Venkataramaiah Chintha,et al.  Green synthesis, molecular docking, anti-oxidant and anti-inflammatory activities of α-aminophosphonates , 2019, Medicinal Chemistry Research.

[2]  B. Hari,et al.  Tungstosulfonic acid-catalyzed green synthesis and bioassay of α-aminophosphonates , 2019, Monatshefte für Chemie - Chemical Monthly.

[3]  N. Chamarthi,et al.  Nano Sb2O3 catalyzed green synthesis, cytotoxic activity, and molecular docking study of novel α-aminophosphonates , 2019, Medicinal Chemistry Research.

[4]  A. Gerasimov,et al.  The Pudovik reaction: the synthesis of bioactive α-aminophosphonates with long alkyl chains , 2019, Phosphorus, Sulfur, and Silicon and the Related Elements.

[5]  C. S. Reddy,et al.  Palladium acetate-catalysed one-pot green synthesis of bis α-aminophosphonates , 2018, Research on Chemical Intermediates.

[6]  C. S. Reddy,et al.  Nano-Cuo–Au-catalyzed solvent-free synthesis of α-aminophosphonates and evaluation of their antioxidant and α-glucosidase enzyme inhibition activities , 2018 .

[7]  Narasimha Golla,et al.  Ethyl phosphoramidates of acyclovir: design, synthesis, molecular docking (HN Protein), and evaluation of antiviral and antioxidant activities , 2017, Medicinal Chemistry Research.

[8]  N. B. Reddy,et al.  Cellulose-SO3H catalyzed synthesis of bis(α-aminophosphonates) and their antioxidant activity , 2017 .

[9]  I. Csontos,et al.  The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction , 2017, Beilstein journal of organic chemistry.

[10]  N. Revaprasadu,et al.  Design, green synthesis, anti-microbial, and anti-oxidant activities of novel α-aminophosphonates via Kabachnik-Fields reaction , 2016 .

[11]  P. V. G. Reddy,et al.  Efficient solvent free synthesis of tertiary α-aminophosphonates using H2Ti3O7 nanotubes as a reusable solid-acid catalyst , 2015 .

[12]  T. Ali,et al.  Methods for the synthesis of α-heterocyclic/heteroaryl- α-aminophosphonic acids and their esters , 2015 .

[13]  S. K. Ghosh,et al.  Didanosine phosphoramidates: synthesis, docking to viral NA, antibacterial and antiviral activity , 2014, Medicinal Chemistry Research.

[14]  Hengshan Wang,et al.  Synthesis and antitumor activities of novel thiourea α-aminophosphonates from dehydroabietic acid. , 2013, European journal of medicinal chemistry.

[15]  M. Sieńczyk,et al.  Human neutrophil elastase phosphonic inhibitors with improved potency of action. , 2012, Journal of medicinal chemistry.

[16]  C. Cativiela,et al.  An Overview of Stereoselective Synthesis of α-Aminophosphonic Acids and Derivatives. , 2009, Tetrahedron.

[17]  K. Troev,et al.  Recent synthesis of aminophosphonic acids as potential biological importance , 2010, Amino Acids.

[18]  Pinaki S. Bhadury,et al.  Synthesis and antiviral activities of amide derivatives containing the alpha-aminophosphonate moiety. , 2008, Journal of agricultural and food chemistry.

[19]  J. Balzarini,et al.  Eco-friendly synthesis and biological evaluation of new quinoline-based dialkyl alpha-aminophosphonates , 2007 .

[20]  Forest Rohwer,et al.  Here a virus, there a virus, everywhere the same virus? , 2005, Trends in microbiology.

[21]  M. Mayo.  A summary of taxonomic changes recently approved by ICTV , 2002, Archives of Virology.

[22]  S. Benkovic,et al.  Peptide bond formation via catalytic antibodies: Synthesis of a novel phosphonate diester hapten , 1994 .

[23]  S. Benkovic,et al.  Peptide synthesis catalyzed by an antibody containing a binding site for variable amino acids. , 1994, Science.

[24]  R. Lamb.  Paramyxovirus fusion: a hypothesis for changes. , 1993, Virology.

[25]  Michael J. Miller,et al.  EPSP Synthase: The Design and Synthesis of Bisubstrate Inhibitors Incorporating Novel 3-Phosphate Mimics , 1993 .

[26]  J. H. Boom,et al.  Peptides containing the novel methylphosphinamide transition-state isostere , 1993 .

[27]  P. Wirsching,et al.  Phosphonamidates and phosphonamidate esters as HIV-1 protease inhibitors , 1991 .

[28]  J. Wood,et al.  Renin inhibitors. Synthesis of transition-state analogue inhibitors containing phosphorus acid derivatives at the scissile bond. , 1989, Journal of medicinal chemistry.

[29]  E. Logusch,et al.  Synthesis of .alpha.- and .gamma.-alkyl-substituted phosphinothricins: potent new inhibitors of glutamine synthetase , 1988 .

[30]  P. Bartlett,et al.  Phosphorus amino acid analogues as inhibitors of leucine aminopeptidase. , 1987, Journal of medicinal chemistry.

[31]  B. S. Pomeroy,et al.  An outbreak of conjunctivitis due to Newcastle disease virus (NDV) occurring in poultry workers. , 1952, American journal of public health and the nation's health.