Antistaphylococcal evaluation of indole–naphthalene hybrid analogs

Abstract

Resistance developments against established antibiotics are an emerging problem for antibacterial therapies. Infections with Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) have become more difficult to treat with standard antibiotics that often fail, especially against MRSA. In consequence, novel antibiotics are urgently needed. Antibiotics from natural sources own complicated structures that cause difficulties for a chemical synthetic production. We developed novel small-molecule antibacterials that are easily accessible in a simple one-pot synthesis. The central indolonaphthalene core is substituted with indole residues at various positions. Both the varied indole substitutions and their positions at the molecular scaffold influence the determined antibacterial activity against the evaluated Staphylococcus strains. Best activities have been found for 5-chloro, -cyano, and -hydroxyl indole substitutions. Therefore, first promising lead compounds could be identified that are nontoxic in human HEK and SH-SY5Y cells and exceed the activity of used standard antibiotics, especially against MRSA.

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“…In vitro testing was done on the antibacterial effectiveness of the hybrids (Figure 3) against Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA). According to the findings of this study [7], the hybrids with the best antibacterial property had 5-hydroxy-, 5-cyano-, or 5-chloroindole in their frameworks. Chopra et al [8] created a novel naphthylamine analogs with a substituted azetidin-2-one ring.…”

“…This phenomenon necessitates further research and innovation of potential antibacterial medications capable of battling these resistant strains [6]. In this concern, many researchers have looked at the antibacterial effect of grafting various cyclic moieties with albocarboncontaining compounds [7][8][9][10][11][12][13][14][15]. Many functionalized indoles were synthesized by Ashraf et al and grafted to the albocarbon nucleus.…”

Recent advances in indole dimers and hybrids with antibacterial activity against methicillin‐resistant Staphylococcus aureus

“…[ 47 ] The naphthalene‐containing indole dimers 21 (MIC: 5.0–522 µg/ml) and 22 (MIC: 11–193 µg/ml) were sensitive to S. aureus and MRSA, and the most active dimer 21a (MIC: 5.0 µg/ml) was comparable to linezolid (MIC: 6.0 µg/ml) and vancomycin (MIC: 3.0 µg/ml) against the two strains, and it was 9.6‐fold more potent than oxacillin (MIC: 48 µg/ml) against MRSA. [ 48 ] In addition, this dimer was nontoxic toward human HEK and SH‐SY5Y cells. Thus, dimer 21a could serve as a lead compound for further exploitations.…”