New 1,3-oxazolylphosphonium Salts as Potential Biocides: QSAR Study, Synthesis, Antibacterial Activity and Toxicity Evaluation

Abstract

Background: Due to the increase of multidrug-resistant microorganisms, the search for biologically active molecules does not stop. In the present study, we developed the effective QSAR model which allows a quick search of new potential Staphylococcus aureus inhibitors in the series of quaternary phosphonium salts. A number of the most promising 1,3-oxazol-4-yltriphenylphosphonium derivatives with predicted activities were synthesized and examined to confirm their antibacterial properties and the accuracy of the forecast. Furthermore, the toxicity of the investigated compounds was evaluated. Methods: The predictive QSAR model was developed using Artificial Neural Network approach. Antibacterial properties of the investigated compounds were performed using standard disk diffusion method. The toxicity of the compounds was determined in vivo using zebrafish (Danio rerio) and in vitro on acetylcholinesterase (AChE) enzyme as the test models. Results: The predictive ability of the regression model was tested by cross-validation, giving the cross-validated coefficient q2=0.82. Derivatives of 1,3-oxazol-4-yltriphenylphosphonium salts predicted as active were synthesized and screened for their antibacterial activities. All compounds demonstrated antibacterial activity according to the prediction. The toxicity tests indicated that all investigated samples were less toxic than well-known cationic surfactants. Conclusion: The most promising compound 2b exhibited strong antibacterial activity together with low toxicity and can be considered as a new efficient biocidal agent for future investigation. In addition, the proposed QSAR model can be used for predicting and designing novel potential S. aureus inhibitors among ionic liquids/salts.

In silico and in vitro studies of a number PILs as new antibacterials against MDR clinical isolate Acinetobacter baumannii

“…They are used for imaging and diagnosing tumors, and also as anticancer (Madar et al, 2007), antioxidant (Sheu, Nauduri, & Anders, 2006), antiviral, and antiparasitic agents (Spivak et al, 2014). PILs are also used extensively to fight bacterial and fungal infections (Trush et al, 2018). and additionally as biocides and antifouling agents (Joseph et al, 2016).…”

A review of recent advances towards the development of QSAR models for toxicity assessment of ionic liquids

“…Substances of interest were synthesized and screened for their antibacterial activity towards Staphylococcus aureus ATCC 25923 and Staphylococcus. According to performed antibacterial tests all compounds demonstrated the expected activity towards bacteria (Holovchenko et al, 2018).…”

“…Authors demonstrated that RBN and Mv of HBD compounds showed positive effects on cytotoxicity of tested ILs, then the molar ratio of HBA to HBD and the number of HBD carbons exhibited the negative impact on activity of ILs. Models of minimal inhibitory concentration (Holovchenko et al, 2018) were developed based on data for 242 ILs from the OCHEM database (Sushko et al, 2011). According to the predictions obtained, the authors (Holovchenko et al, 2018) supposed that 1,3-oxazol-4-yl(triphenyl)phosphonium derivatives have antibacterial activities.…”

“…Models of minimal inhibitory concentration (Holovchenko et al, 2018) were developed based on data for 242 ILs from the OCHEM database (Sushko et al, 2011). According to the predictions obtained, the authors (Holovchenko et al, 2018) supposed that 1,3-oxazol-4-yl(triphenyl)phosphonium derivatives have antibacterial activities. Substances of interest were synthesized and screened for their antibacterial activity towards Staphylococcus aureus ATCC 25923 and Staphylococcus.…”

1,3-Oxazol-4-ylphosphonium salts as new non-peptide inhibitors of furin

“…One of these groups is the lipophilic triphenyl-phosphonium (TPP) ion [30][31][32]. Indeed, the derivatives, bearing quaternary phosphonium salts were reported to show high antimicrobial activities [33][34][35] so that these cations were considered as a new generation of effective antiseptics. As pharmacological agents, TPP salts found to have also antiglycemic properties [36] and antiproliferative [36], antioxidant [37], antiviral activities [34].…”