3,4,5,3’,5’-pentabromo-2-(2’-hydroxybenzoyl) pyrrole: a potential lead compound as anti Gram-positive and anti biofilm agent

The activity against Gram-positive bacteria of 3,4,5,3 ,5 -pentabromo-2-(2 -hydroxybenzoyl)pyrrole I, a synthetic anti-bacterial compound related to pyrrolomycins, was tested in vitro using seven reference bacterial strains and Staphylococcus epidermidis and Staphylococcus aureus preformed biofilms. Compound I was active against all strains tested, with minimum inhibitory concentration (MIC) values ranging from 0.002 to 0.097 mg/l and minimum bactericidal concentrations (MBCs) from 0.37 to 12.5 mg/l. Compound I was also active at low concentrations against preformed S. epidermidis and S. aureus biofilms

Pyrrolomycins as potential anti-staphylococcal biofilms agents

With the goal of discovering new anti-infective agents active against microbial biofilms, we focused on some natural pyrrolomycins, a family of halogenated pyrrole antibiotics. In this study we investigated the anti-staphylococcal biofilm activity of pyrrolomycins C, D, F1, F2a, F2b, F3 and of the synthesized related compounds I, II, III. The susceptibility of six staphylococcal biofilms was determined by methyltiazotetrazolium (MTT) staining. Most of the compounds were active at concentrations of 1.5 μg/mL with significant inhibition percentages. A few of the compounds were active at the lowest screening concentration of 0.045μg/mL. We also report the population log reduction of activity against the two best biofilm forming S. aureus strains as determined by viable plate counts. In order to adequately assess the utility of these compounds, their toxicity against human cells was evaluated. In conclusion, pyrrolomycins and synthetic derivatives are promising compounds for developing novel effective chemical countermeasures against staphylococcal biofilm

Synthesis and Anti-Staphylococcal Activity of New Halogenated Pyrroles Related to Pyrrolomycins F

The chemical synthesis of new halogenated pyrroles related to pyrrolomycins F is described and the anti-staphylococcal activity compared. The replacement of 4′-bromo atom of parent compounds with two chloro atoms at 3′ and 5′ position increase the antibacterial activity against a reference strain of S. aureus

Synthesis and antimicrobial activity of new bromine-rich pyrrole derivatives related to monodeoxypyoluteorin

The synthesis and antimicrobial activity of new pyrrole derivatives structurally related to monodeoxypyoluteorin are described. The insertion of a keto or methylene spacer between the phenol group and the pyrroloyl moiety of brominated 2-(2′-hydroxybenzoyl)pyrroles leads to a decrease of the antibacterial activity

Novel chemical countermeasures against staphylococcal biofilms

Some natural and synthetic related pyrrolomycins, a family of halogenated pyrrole antibiotics, showed anti-biofilm properties in vitro at low concentration (0.045μg/mL) against preformed staphylococcal biofilms. Moreover, considering the human cell toxicity, the selectivity indexes (ratio of cytotoxicity to antibiofilm activity) of some of them were very interesting. The present study aims to investigate if the pyrrolomycins could also prevent staphylococcal biofilm formation. The evaluation of S.aureus ATCC 25923 biofilm formation inhibition was conducted by safranin staining method. At tested concentrations of 0.18, 0.09, 0.045 μg/mL (concentrations much lower than MIC value determined on planktonic strain) the novel pyrrolomycin derivative IV resulted effective as biofilm inhibitor showing inhibition percentages ranging from 56.5 to 29% against S.aureus ATCC 25923. We are investigating if sortase A which is responsible for the anchoring of surface proteins to Gram positive cell wall, could be the rational target of pyrrolomycins. The surface proteins play pivotal roles in the adhesion to host’s tissues, and the evasion of host-immune responses, moreover they facilitate attachment on biological and abiotic surfaces in the first steps of biofilm formation. It has been observed that inhibition of sortase A by different chemicals resulted in decrease of virulence and staphylococcal biofilm formation. A molecular modeling study conducted by using a crystal structure of sortase A, recovered from protein data bank, and by studying docking properties of a known sortase A inhibitor and of pyrrolomycins, is in progress. In vitro experiments on sortase inhibition activity are needed to confirm the computational result