Saiful Azmi Johari: Antimicrobial Laboratory, Anti-Infective Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia. ORCID
Mastura Mohtar: Antimicrobial Laboratory, Anti-Infective Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia.
Sharifah Aminah Syed Mohamad: Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia.
Mohd Fazli Mohammat: Organic Synthesis Laboratory, Institute of Science, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia.
Rohana Sahdan: Biotherapeutic Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia.
Azman Mohamed: Biotherapeutic Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia.
Mohamad Jemain Mohamad Ridhwan: Biotherapeutic Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia.
Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC values at >625 g/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates.
