title: In vitro inhibitory and cytotoxic activity of MFM 501, a novel codonopsinine derivative, against Methicillin-Resistant Staphylococcus aureus clinical isolates.
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.
authors.affiliation: Antimicrobial Laboratory, Anti-Infective Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia ; Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Saiful Azmi
authors.initials: SA
authors.lastname: Johari
authors.affiliation: Antimicrobial Laboratory, Anti-Infective Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia.
authors.forename: Mastura
authors.initials: M
authors.lastname: Mohtar
authors.affiliation: Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Sharifah Aminah Syed
authors.initials: SA
authors.lastname: Mohammad
authors.affiliation: Biotherapeutic Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia.
authors.forename: Rohana
authors.initials: R
authors.lastname: Sahdan
authors.affiliation: Organic Synthesis Laboratory, Institute of Science, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Zurina
authors.identifier: 0000-0002-0314-8532
authors.initials: Z
authors.lastname: Shaameri
authors.affiliation: Organic Synthesis Laboratory, Institute of Science, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Ahmad Sazali
authors.initials: AS
authors.lastname: Hamzah
authors.affiliation: Organic Synthesis Laboratory, Institute of Science, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Mohd Fazli
authors.initials: MF
authors.lastname: Mohammat
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D055624:Methicillin-Resistant Staphylococcus aureus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D011759:Pyrrolidines; C415669:codonopsinine