Novel R-plasmid conjugal transfer inhibitory and antibacterial activities of phenolic compounds from Mallotus philippensis (Lam.) Mull. Arg.

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.

The Glasgow Prognostic Score (GPS) predicts toxicity and efficacy in platinum-based treated patients with metastatic lung cancer.

PURPOSE: Lung cancer is the most common cause of cancer death. A cumulative prognostic score based on C-reactive protein and albumin, termed the Glasgow Prognostic Score (GPS), indicates the presence of systemic inflammatory response. GPS has been proposed as a powerful prognostic tool for patients with various types of malignant tumors, including lung cancer. The aim of this study was to assess the predictive value of baseline GPS in terms of toxicity and response in lung cancer patients treated with platinum-based chemotherapy. PATIENTS AND METHODS: Patients referred to our institution for consideration of first-line platinum-based treatment were eligible. Demographics and disease-related characteristics were recorded. Toxicity was graded according to NCI CTCAE version 3.0 throughout first-line therapy. GPS was calculated before the onset of treatment and was related to the development of toxicity. Response to first-line therapy and survival data were also collected. RESULTS: Totally, 96 lung cancer patients were accrued. GPS was associated with increased mucositis p=0.004), neurotoxicity (p=0.038), neutropenia (p=0.02), dose reductions or/ and need for granulocyte colony-stimulating factor (G-CSF) support (p=0.005), toxicity-related termination of treatment (p=0.001) and chemotherapy-related toxic deaths (p=0.013). GPS was associated with overall survival (p=0.016) and progression-free survival (p=0.016) as well as response to treatment (p=0.05). CONCLUSIONS: Our data demonstrate that GPS assessment is predictive of the most important aspects of platinum-related toxicity and this may partly explain its associations with poor clinical outcome in patients with metastatic lung cancer.