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

Abstract

This work presents the successful synthesis of a library of novel peptidomimetics via Ugi multicomponent reaction. Most of these peptidomimetics contain differently substituted aminocoumarin; 7-amino-4-methylcoumarin and 7-amino-4-(trifluoromethyl) coumarin. Inspired by the biological properties of coumarin derivatives and peptidomimetics, we proposed the synthesis of coumarin incorporated peptidomimetics. We studied the potential of synthesized compounds as antimicrobial drugs on model E. coli bacterial strains (k12 and R2–R4). To highlight the importance of coumarin in antimicrobial resistance, we also synthesized the structurally similar peptidomimetics, using benzylamine. Preliminary cellular studies suggest that the compounds with coumarin derivatives have more potential as antimicrobial agents compared to the compounds without coumarin. We also analyzed the effect of aldehyde, free acid group and ester group on the course of their antimicrobial properties.

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

“…As in previous studies on various types of compounds, we also wanted to observe the effect of modification on the magnitude of oxidative damage, which should be seen as extending strands compared to unmodified forms having the three forms ccc, oc and linear. What has been observed in previous studies [41][42][43][44][45][46][47][48][49]. The results of bacterial DNA modified with amidoxime is shown in Figure 6 (with the action of Fpg), and in Supplementary Materials Figures S1 and S2.…”

“…The changes in the main topological forms of the plasmid: ccc, oc and linear were observed in DNA isolated from model strains and digested with Fpg protein. About 4% of oxidative damage was identified after digestion with the Fpg protein, which indicates that the analyzed compounds damage bacterial DNA very strongly due to the oxidative stress induced by them in the cell [41][42][43][44][45][46][47][48][49]. Our observations indicate that the length of the alkyl chain of peptidomimetics may determine the toxicity to some E. coli R4 strains, as evidenced by the MIC and MBC values [50].…”

“…The microbiological analysis procedures have been carefully described in the literature citations [41][42][43][44][45][46][47][48][49].…”

Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives

“…Modified bacterial DNA was digested by using Fpg protein. We wanted to observe whether the resulting modifications in bacterial DNA would introduce oxidative damage to the DNA chain by changing the topological three forms [ 50 , 57 , 58 , 59 , 60 , 61 , 62 ]. Probably the size of the specific substituent at α-position may determine the toxicity of the analyzed E. coli strains, including in particular R4, as evidenced by the obtained MIC and MBC values.…”

“…Among the derivatives studied, the compounds possessing methyl group at α-position 5 , 6 , 7 , 8, and 9 turned out to be the most active comparing to derivatives with aryl group at α-position ( Figure 2 ). The research results presented are important for understanding the biological properties of tested α-hydroxy phosphonate derivatives as a function of potential new antibiotics and their toxic effects on Gram-negative bacteria in the face of the growing drug resistance pandemic, in reference to our previous works related to the characteristics of the model E.coli K12 and R2-R4 [ 44 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. Finally, the analyzed α-hydroxy phosphonate derivatives are more cytotoxic in the model bacterial cells than the commonly used antibiotics: ciprofloxacin, bleomycin, and cloxacillin.…”