In vitro inhibitory and cytotoxic activity of MFM 501, a Novel codonopsinine derivative, against methicillin-resistant Staphylococcus aureus clinical isolates

• Main Authors: Hamzah, A.S (Author), Johari, S.A (Author), Mohammat, M.F (Author), Mohtar, M. (Author), Sahdan, R. (Author), Shaameri, Z. (Author), Syed Mohammad, S.A (Author)
• Format: Article
• Language: English
• Published: Hindawi Publishing Corporation 2015
• Subjects: alkaloid; Alkaloids; Anti-Bacterial Agents; antibiotic agent; antiinfective agent; apoptosis; Apoptosis; Article; bactericidal activity; bacteriostasis; bacterium isolation; cell survival; Cell Survival; chemistry; clinical evaluation; codonopsinine; controlled study; cytology; cytotoxicity; dose response; Dose-Response Relationship, Drug; drug effects; drug safety; drug screening; IC50; in vitro study; in vivo study; methicillin resistant Staphylococcus aureus; methicillin susceptible Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus; mfm 501; microbial sensitivity test; Microbial Sensitivity Tests; minimum bactericidal concentration; minimum inhibitory concentration; nonhuman; physiology; pyrrolidine derivative; Pyrrolidines; reaction analysis; Staphylococcus aureus; structure activity relation; unclassified drug
• Online Access: View Fulltext in Publisher; View in Scopus

 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 g/mL against 55 S. aureus isolates (43 MRSA and 12 MSSA isolates). The active compound also displayed MBC values between 250 and 500 g/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. © 2015 Saiful Azmi Johari et al.