Synthesis of new bioactive aminophosphonates and study of their antioxidant, anti-inflammatory and antibacterial activities as well the assessment of their toxicological activity Rebiha Damiche * , Salah Chafaa Laboratory of Electrochemical Molecular Materials and Complex LEMMC, Department of Process Engineering, Faculty of Technology, University Ferhat ABBAS Setif -1, El-Maabouda, 19000, Setif, Algeria article info Article history: Received 8 May 2016 Received in revised form 16 October 2016 Accepted 16 October 2016 Available online 17 October 2016 Keywords: Synthesis a-aminophosphonates Bioactive molecules Antioxidant Cytotoxicity DPPH abstract Two new categories of a-aminophosphonates molecules were synthesized and characterized by UV-Vis, IR, and NMR. Their spectral properties show a perfect convergence. Their biological activities were evaluated. Molecules 1a, 2a, and 1d present a greater antioxidant potential than BHT and vitamin C. The best anti-inflammatory activity is shown by the 2b molecule and that of 1a, 2a, and 2c molecules are closely comparable to that of diclofenac. The antibacterial activity of the synthesized compounds is significantly higher than the antibiotic amoxicillin. The hemolysis rate HR of compounds 1b, 1c, 2b, and 2c was lower than 5%. © 2016 Published by Elsevier B.V. 1. Introduction Organophosphorus compounds have a wide application in the industry [1], medicinal chemistry [2]. In recent years, the synthesis of phosphonates compounds has attracted significant attention, due to their multiple uses in many vital areas [3,4]. a-aminophosphonates are the analogs of natural amino acid [5,6] and some of them exhibit broad-spectrum biological activ- ities, such as anti-HIV, antibiotic, antibacterial, and antiviral agents, anticancer [7], inhibition of activities of enzymes [8] and anti-virus activities [9]. Furthermore, a-aminophosphonates are used in agricultural industry as fungicidal, herbicidal agents and plant growth regulators [10e12]. a-Aminophosphonates usually have lower toxicities and resid- ual effects on mammalian. On the other hand, some highly bioac- tive compounds contain cyclopropane moiety used as commercial insecticide pyrethroids [13], KARI inhibitors showing antifungal activities [14,15], etc. As a result, several of synthetic approaches have been developed for the synthesis of a-aminophosphonates [16]. Among them, Kabachnik-Fields three-component reaction, in which an amine, an aldehyde, and dialkylphosphite are reacted in one-pot set-up, is an important one. In few reports, this reaction was carried out in straightforward one-pot procedures without any catalysts [17]. While, in most cases it was performed using catalysts, such as LiClO 4 [18,19], TaCl 5 eSiO 2 [20], InCl 3 [21], lanthanide-triflate and CF 3 COOH. The key step in this synthesis is the nucleophilic addition of a carbonyl compound to amine followed by addition of a diaryl (or) dialkylphosphite to the resulting imine. Formation of hydroxyl phosphonates and product of rearrangement frequently accom- pany this reaction. In view of the greater applicability of a-ami- nophosphonates, an easy one-pot synthesis process for them has been developed by Kabachnik-Fields reaction under mild condi- tions without a catalyst. In our laboratory, we have contributed to the enrichment of organophosphorus compounds by a synthesis of a new generation of (o-hydroxyphenyl) methylphosphonic acid [22,23] and recently by a series of aminophenol derivatives [24]. Considering the biological importance of phosphorylated com- pounds, we turned our attention here to the synthesis of a new series of a-aminophosphonates of propylamine and para-amino- pyridine derivatives in toluene without a catalyst. All the * Corresponding author. E-mail address: damicherebiha@gmail.com (R. Damiche). Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: http://www.elsevier.com/locate/molstruc http://dx.doi.org/10.1016/j.molstruc.2016.10.054 0022-2860/© 2016 Published by Elsevier B.V. Journal of Molecular Structure 1130 (2017) 1009e1017