ARTICLE | doi:10.20944/preprints202108.0081.v1
Subject: Life Sciences, Biochemistry Keywords: heteroaromatic stilbene derivatives; antimicrobial activity; Staphylococcus aureus; Enterococcus faecalis; Escherichia coli; Pseudomonas aeruginosa; Acinetobacter baumannii; Klebsiella pneumoniae.
Online: 3 August 2021 (13:32:14 CEST)
The widespread use of antibiotics has led to a gradual increase in drug-resistant bacterial infections, which severely weakens the clinical efficacy of antibacterial therapies. In recent decades, stilbenes aroused great interest because of their high bioavailability, as well as for their manifold biological activity. Our research efforts are focused on synthetic heteroaromatic stilbene deriva-tives as they represent a potentially new type of antibiotic with a wide antibacterial spectrum. Herein, a preliminary molecular modeling study and a versatile synthetic scheme allowed us to define eight heteroaromatic stilbene derivatives with potential antimicrobial activity. In order to evaluate our compound’s activity spectrum and antibacterial ability, Minimum Inhibitory Con-centration (MIC) and Minimum Bactericidal Concentration (MBC) tests have been performed on Gram-positive and Gram-negative ATCC strains. Compounds PB4, PB5, PB7 and PB8 showed the best values in terms of MIC and were also evaluated for MBC, which however was found to be greater than MIC, confirming a bacteriostatic activity. For all compounds, we evaluated toxici-ty on colon-rectal adenocarcinoma cells tumor cells (CaCo2), once established that the whole se-lected set was more active than 5-Fluorouracil in reducing CaCo-2 cells viability. To the best of our knowledge, the biological assays have shown for these derivatives an excellent bacteriostatic activity, compared to similar molecular structures previously reported, thus paving the way for a new class of antibiotic compounds.
ARTICLE | doi:10.20944/preprints202205.0175.v1
Subject: Life Sciences, Microbiology Keywords: ESKAPE; heteroaryl-ethylenes; clinical strains; antimicrobial activity
Online: 13 May 2022 (03:30:57 CEST)
The World Health Organization has identified antimicrobial resistance as a public health emergency and developed a global priority pathogens list of antibiotic-resistant bacteria that can be summarized in the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales species), reminding us of their ability to escape the effect of antibacterial drugs. We previously tested new heteroaryl-ethylene compounds in order to define their spectrum of activity and antibacterial capability. Now, we focus our attention on PB4, a compound with promising MIC and MBC values in all conditions tested. In the present study, we evaluate the activity of PB4 on selected samples of ESKAPE isolates from nosocomial infections: 14 S. aureus, 6 E. faecalis, 7 E. faecium, 12 E. coli and 14 A. baumanii. Furthermore, an ATCC control strain was selected for all species tested. MICs were performed according to the standard method, with some modifications. PB4 MIC values were within very low ranges regardless of bacterial species and resistance profiles: from 0,12 to 2 mg/L for S. aureus, E. faecalis, E. faecium and A. baumannii. For E. coli, the MIC values obtained were slightly higher (4-64 mg/L), butstill promising. The PB4 heteroaryl-ethylenic compound was able to counteract the bacterial growth of both high-priority Gram-positive and Gram-negative clinical strains. In the future, it would be interesting to evaluate the activity of PB4 in animal models to test for its toxicity.