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BioMed Research International
Volume 2015 (2015), Article ID 823829, 9 pages
http://dx.doi.org/10.1155/2015/823829
Research Article

In Vitro Inhibitory and Cytotoxic Activity of MFM 501, a Novel Codonopsinine Derivative, against Methicillin-Resistant Staphylococcus aureus Clinical Isolates

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
3Biotherapeutic Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia
4Organic Synthesis Laboratory, Institute of Science, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia

Received 18 July 2014; Revised 4 November 2014; Accepted 13 November 2014

Academic Editor: Frederick D. Quinn

Copyright © 2015 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

28 new pyrrolidine types of compounds as analogues for natural polyhydroxy alkaloids of codonopsinine were evaluated for their anti-MRSA activity using MIC and MBC value determination assay against a panel of S. aureus isolates. One pyrrolidine compound, MFM 501, exhibited good inhibitory activity with MIC value of 15.6 to 31.3 μg/mL against 55 S. aureus isolates (43 MRSA and 12 MSSA isolates). The active compound also displayed MBC values between 250 and 500 μg/mL against 58 S. aureus isolates (45 MRSA and 13 MSSA isolates) implying that MFM 501 has a bacteriostatic rather than bactericidal effect against both MRSA and MSSA isolates. In addition, MFM 501 showed no apparent cytotoxicity activity towards three normal cell lines (WRL-68, Vero, and 3T3) with IC50 values of >625 µg/mL. Selectivity index (SI) of MFM 501 gave a value of >10 suggesting that MFM 501 is significant and suitable for further in vivo investigations. These results suggested that synthetically derived intermediate compounds based on natural products may play an important role in the discovery of new anti-infective agents against MRSA.