Amphiphilic cyclic peptide [W4R4] showed antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 4 µg/mL Herein, we hypothesized that conjugation or combination of the lead peptide with levofloxacin could improve the antibacterial activity of levofloxacin. Levofloxacin-[R4W4] and Q-levofloxacin-[R4W4] were synthesized, and their antibacterial activities were compared with the corresponding physical mixtures and parent compounds against MRSA. Although Q-levofloxacin was inactive even at a concentration of 128 µg/mL, Q-levofloxacin-[R4W4] and the corresponding physical mixture showed MIC values of 8 µg/mL, possibly due to the activity of the peptide. On the other hand, levofloxacin-[R4W4] conjugate (MIC = 32 µg/mL) and the corresponding physical mixture (MIC = 8 µg/mL) was less active than levofloxacin (MIC = 2 µg/mL). The data showed that the conjugation of levofloxacin with [R4W4] significantly reduced the antibacterial activity compared to the parent analogs, while Q-levofloxacin-[R4W4] conjugate was more potent than Q-levofloxacin alone.

Synthesis and evaluation of antimicrobial activity of levofloxacin-[R4W4] and Q-levofloxacin-[R4W4] conjugates and comparison with the corresponding physical mixtures

253rd National Meeting (2017)

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