Synthesis and anti‐staphylococcal activity of new halogenated pyrroles related to Pyrrolomycins F

Abstract

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.

In vitro anti-Gram-positive and antistaphylococcal biofilm activity of newly halogenated pyrroles related to pyrrolomycins

“…Recently, Dubois et al described a clinical strain of E. coli producing OXA-30 (now known to be identical to OXA-1) with decreased susceptibility (MIC = 4 mg/L) but not highlevel resistance to cefepime [5,6]. Like us, they were unable to demonstrate any outer membrane porin deficiency in their strain.…”

“…1), synthesised and characterised by us [6] and related to pyrrolomycins B-E, were potential agents with improved antibacterial and antibiofilm activity against a panel of Gram-positive and staphylococcal biofilms.…”

Pharmaceutical Potential of Synthetic and Natural Pyrrolomycins

“…The structural changes generated compounds with less antimicrobial activity with respect to compound 4; nevertheless, compounds 18a,b and 19a,b resulted more active on S. aureus than the comparator amikacin, as shown in Table 8. Moreover, the Authors reported the synthesis of new halogenated pyrroles related to pyrrolomycins F 20a-e to investigate their anti-Gram-positive and anti-staphylococcal activities and their ability to inhibit the formation of biofilms (Figure 7) [39,40,53]. Moreover, the Authors reported the synthesis of new halogenated pyrroles related to pyrrolomycins F 20a-e to investigate their anti-Gram-positive and anti-staphylococcal activities and their ability to inhibit the formation of biofilms (Figure 7) [39,40,53].…”

“…Moreover, the Authors reported the synthesis of new halogenated pyrroles related to pyrrolomycins F 20a-e to investigate their anti-Gram-positive and anti-staphylococcal activities and their ability to inhibit the formation of biofilms (Figure 7) [39,40,53]. Moreover, the Authors reported the synthesis of new halogenated pyrroles related to pyrrolomycins F 20a-e to investigate their anti-Gram-positive and anti-staphylococcal activities and their ability to inhibit the formation of biofilms (Figure 7) [39,40,53]. (compounds 18a,b and 19a,b) to investigate whether the introduction of a keto or methylene spacer between the phenol and pyrroloyl moiety led to more active compounds [52].…”

“…The introduction of halogen atoms on the pyrrole moiety was conducted by addition of the appropriate equivalents of N-bromosuccinimide or N-chlorosuccinimide in acetonitrile. Finally, the demethylation using anhydrous aluminum chloride in dry dichloromethane led to compounds 20a-e [53]. Results showed that the replacement of the 4 1 -bromo atom on the phenolic ring of pyrrolomycins F with two chloro atoms at the 3 1 and 5 1 position resulted in an increase of antibacterial activity against all strains tested, with MIC values ranging from ď0.001 to 12.5 µg/mL and MBC values ranging from ď0.39 µg/mL to 12.5 µg/mL.…”