title: Novel R-plasmid conjugal transfer inhibitory and antibacterial activities of phenolic compounds from Mallotus philippensis (Lam.) Mull. Arg.
abstract: Antimicrobial resistance severely limits the therapeutic options for many clinically important bacteria. In Gram-negative bacteria, multidrug resistance is commonly facilitated by plasmids that have the ability to accumulate and transfer refractory genes amongst bacterial populations. The aim of this study was to isolate and identify bioactive compounds from the medicinal plant Mallotus philippensis (Lam.) Mull. Arg. with both direct antibacterial properties and the capacity to inhibit plasmid conjugal transfer. A chloroform-soluble extract of M. philippensis was subjected to bioassay-guided fractionation using chromatographic and spectrometric techniques that led to the isolation of the known compounds rottlerin [5,7-dihydroxy-2,2-dimethyl-6-(2,4,6-trihydroxy-3-methyl-5-acetylbenzyl)-8-cinnamoyl-1,2-chromene] and the red compound (8-cinnamoyl-5,7-dihydroxy-2,2,6-trimethylchromene). Both compounds were characterised and elucidated using one-dimensional and two-dimensional nuclear magnetic resonance (NMR). Rottlerin and the red compound showed potent activities against a panel of clinically relevant Gram-positive bacteria, including meticillin-resistant Staphylococcus aureus (MRSA). No significant direct activities were observed against Gram-negative bacteria. However, both rottlerin and the red compound strongly inhibited conjugal transfer of the plasmids pKM101, TP114, pUB307 and R6K amongst Escherichia coli at a subinhibitory concentration of 100mg/L. Interestingly, despite the planar nature of the compounds, binding to plasmid DNA could not be demonstrated by a DNA electrophoretic mobility shift assay. These results show that rottlerin and the red compound are potential candidates for antibacterial drug lead development. Further studies are needed to elucidate the mode of inhibition of the conjugal transfer of plasmids.
authors.affiliation: Research Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Blessing O M
authors.initials: BO
authors.lastname: Oyedemi
authors.affiliation: Department of Pharmacognosy, Poona College of Pharmacy, Pune 38, India.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Shinde
authors.affiliation: Department of Pharmacognosy, Poona College of Pharmacy, Pune 38, India.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Shinde
authors.affiliation: Research Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Dionysia
authors.initials: D
authors.lastname: Kakalou
authors.affiliation: Research Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Stapleton
authors.affiliation: Research Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK. Electronic address: simon.gibbons@ucl.ac.uk.
authors.forename: Simon
authors.initials: S
authors.lastname: Gibbons
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D036461:Mallotus Plant / Q000737:chemistry*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts; D011815:R Factors / Q000235:genetics*
chemical_list: D000098:Acetophenones; D000900:Anti-Bacterial Agents; D001578:Benzopyrans; D010636:Phenols; D010936:Plant Extracts; C085746:rottlerin
keywords: Anti-plasmid; Antibacterial agent; Bacterial plasmids; Conjugation; Multidrug resistance; Natural products