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BioMed Research International
Volume 2017, Article ID 8032865, 10 pages
https://doi.org/10.1155/2017/8032865
Research Article

In Vitro Evaluations and In Vivo Toxicity and Efficacy Studies of MFM501 against MRSA

1Antimicrobial Laboratory, Anti-Infective Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia
2Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia
3Organic Synthesis Laboratory, Institute of Science, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia
4Biotherapeutic Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia
5Pharmacy Programme, Sultan Azlan Shah Allied Health Sciences College, 31250 Tanjung Rambutan, Perak, Malaysia

Correspondence should be addressed to Saiful Azmi Johari; ym.vog.mirf@imzalufias

Received 9 January 2017; Revised 4 March 2017; Accepted 9 March 2017; Published 27 April 2017

Academic Editor: Paul M. Tulkens

Copyright © 2017 Saiful Azmi Johari et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo 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 log10 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 (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) 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.