Ferrocenyl chalcone derivatives as possible antimicrobial agents

Abstract

The swift spread of infections caused by drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has quickly become a worldwide concern as infections spread from healthcare settings to the wider community. While ferrocenyl chalcones, which are chalcone derivatives with antimicrobial activity, have gained attention from researchers, further study is needed to assess their cytotoxicity. Ten newly developed chalcones, in which ring A was replaced with a ferrocenyl moiety and ring B contained increasing alkyl chain lengths from 5-10 carbons, were assessed. Using 2-fold broth microdilution, the minimum inhibitory concentration (MIC) of five of the ten compounds were lower against Gram-positive organisms (MICs from 0.008 mg/ml to 0.063 mg/ml) than Gram-negative organisms (MICs = 0.125 mg/ml). These novel ferrocenyl chalcone compounds were effective against 3 types of clinically isolated drug-resistant S. aureus, including a MRSA, and against other non-resistant clinically isolated and laboratory-adapted Gram-positive bacteria. The same compounds inhibited growth in non-resistant bacteria by potentially obstructing cellular respiration in Gram-positive bacteria. Images obtained through scanning electron microscopy revealed fully lysed bacterial cells once exposed to a selected compound that showed activity. The results indicate that these newly developed compounds could be important antimicrobial agents in the treatment of infections from clinically resistant bacteria.

In vitro nematicidal activity of two ferrocenyl chalcones against larvae of Haemonchus contortus (L3) and Nacobbus aberrans (J2)

“…On the one hand, FcC derivatives have a wide spectrum of biological applications over other pathogens such as bacteria; for example, Henry et al . (2020) mention the use of FcC derivatives as possible antimicrobial agents for the treatment of infections caused by clinically resistant bacteria.…”

Novel ferrocenyl chalcone derivatives as antibacterial agents: is there a solution to the problem?

“…These compounds were designated methyl to decyl based on the number of carbons found in each alkyl group. Five of these ferrocenyl chalcone chemicals used in the Henry et al study, i.e., pentyl, hexyl, heptyl, octyl, nonyl and decyl, exhibited antibacterial activity from 0.008 mg/ml to 0.125 mg/ml against Grampositive lab-adapted organisms and resistant and non-resistant Gram-positive clinical isolates [10]. The alkyl groups of saturated, unbranched alkanes are water-insoluble and their hydrophobicity increases as chain length increases, as described by Stoker [20].…”

“…Ferrocenyl chalcone compounds are primarily classi ed into Type I or Type II (Fig. 1), where the carbonyl group could be located near the ferrocenyl ring in Type I compounds and where the carbonyl group can be found near the phenyl ring in Type II [4,10].…”

“…One possible mechanism of action of ferrocenyl chalcones is to obstruct respiratory enzymes found in the electron transport chain, which is located on the bacterial cell membrane [4,10]. Inhibition of bacterial respiration may cause morphological damage to the cell membrane followed by apoptosis.…”

“…Novel substituted ferrocenyl chalcone compounds used in the Henry et al study [10] Ten ferrocenyl chalcone derivatives (Fig. 2), which were provided by Crouch [19], were assessed as novel antimicrobial agents and were highly hydrophobic compounds due to the addition of increasing lengths of alkyl chains, the addition of ferrocene groups, and the substitution of C5 on the benzene rings with nitrogen atom [10].…”