The Synthesis and Evaluation of Amidoximes as Cytotoxic Agents on Model Bacterial E. coli Strains

Abstract

The biological research on newly synthesized amidoximes, Boc-protected amidoximes and Boc-derived amidines, obtained by a reduction of the parent amidoximes is reported, herein. Due to the presence of a free amino group in both amidines and amidoximes, these compounds can undergo various chemical reactions such as N-alkylation and N-acylation. One such reaction is Boc-protection, often used in organic synthesis to protect the amino and imino groups. Until now, Boc-protected amidoximes have not been tested for biological activity. Amidoxime derivatives were tested on bacterial E. coli strains. Initial cellular studies tests and digestion with Fpg after the modification of bacterial DNA, suggest that these compounds may have greater potential as antibacterial agents compared to antibiotics such as ciprofloxacin (ci), bleomycin (b) and cloxacillin (cl). The described compounds are highly specific for pathogenic E. coli strains on the basis of the model strains used and may be used in the future as new substitutes for commonly used antibiotics in clinical and hospital infections in the pandemic era.

Relationship between Structure and Antibacterial Activity of α-Aminophosphonate Derivatives Obtained via Lipase-Catalyzed Kabachnik−Fields Reaction

“…All selected analyzed α-aminophosphonate derivatives ( Figure 6 ), including different types of alkoxy groups, substituents located at the phenyl ring, and the length of the alkyl chain, can strongly change the topology of bacterial DNA. After digestion with Fpg, approximately 3.5% of oxidative damage was identified, which very strongly indicates oxidative damage in bacterial DNA, similar to the previous observations [ 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ]. The different types of alkoxy groups, substituents located at the phenyl ring, and the length of the alkyl affected this outcome ( Figure 6 ).…”

“…The obtained MIC values as well as our previous studies with various types of the analyzed compounds [ 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ] indicate that α-aminophosphonate derivatives also show a strong toxic effect on the analyzed bacterial model strains. The three analyzed compounds were selected for further analysis by modifying their DNA.…”

“…The Kabachnik–Fields reaction is the most efficient method for the formation of carbon−phosphorus bonds using an aldehyde, amine, and H -phosphite. A number of other synthetic approaches have also been reported for the preparation of α-aminophosphonates [ 7 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. These methods are generally conducted in the presence of various organic and inorganic bases [ 56 , 57 , ...…”

“…The three analyzed compounds were selected for further analysis by modifying their DNA. Modified bacterial DNA was digested with Fpg as described earlier [ 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ]. All selected analyzed α-aminophosphonate derivatives ( Figure 6 ), including different types of alkoxy groups, substituents located at the phenyl ring, and the length of the alkyl chain, can strongly change the topology of bacterial DNA.…”

Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in E. coli Strains

“…N,N-Dimethylformamide (DMF) was purchased from Sigma Aldrich (CAS No. 68-12-2, Poznań, Poland), Lanes 1kb-ladder, and Quick Extend DNA ladder (New England Biolabs, Ipswich, MA, USA), with MIC and MBC tests as described in detail in the previous work [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ] and analyzed by the Tukey test indicated by ( p < 0.05): * p < 0.05, ** p < 0.1, *** p < 0.01.…”