Isolation, Characterization and Synthesis of a Phenyl-substituted Pyrrole Isolated from the Flavonoid Fraction of Mānuka Honey

Compound 1, which occurs in the flavonoid fraction of mānuka honey and showed a statistical correlation with the non-peroxide antibacterial activity of the honeys, was extracted from fifteen kilograms of mānuka honey using Amberlite XAD-2 resin and liquid-liquid extraction, and isolated by a combination of Sephadex-LH20 column chromatography and HPLC. Characterization of 1 was achieved by one and 2D- 1H and 13C NMR spectroscopy and GC-MS and 1 was identified as 2-formyl-5-(2-methoxyphenyl)-pyrrole. In addition to 1, two other non-flavonoids were isolated from the flavonoid fraction and their identities confirmed as caffeic acid and p-coumaric acid. Synthesis of 9 (3-hydroxy-1-(2-methoxyphenyl)-3-(oxazol-4-yl) propan-1-one), an intermediate in the route to 1, gave a yield of 67.5% as a pale yellow crystals after crystallization from CH2Cl2/hexane. Synthesis of 1 from 9 only resulted in barely traceable amount of 1. The dominant product after recrystallization from CH2Cl2/hexane was 10 ((E)-1-(2-methoxyphenyl)-3-(oxazol-4-yl)prop-2-en-1-one) which was the dehydrated analogue of 9. The synthesis of 1 was repeated. The product mixture was fractionated on a silica gel column, followed by two cycles of preparative layer chromatography applied to the fractions which contained 1 and yield 0.36 mg of 1 (0.00179 mmol, 0.2%)

Binding Biological Polyanions - Understanding and Controlling Binding Mode in order to Achieve Controlled Nanoscale Assembly

This thesis explores polyanion binding and sensing using varirty of different approaches and aims to understand and manipulate these interactions. Amine-functionalised pyrene derivatives Py-G1 and Py-DAPMA can act as effective heparin sensors in competitive media using a ratiometric fluorescence sensing approach. The assembly of Py-G1 into pre-formed self-assembled multivalent (SAMul) nanostructures provides it with a significant (order of magnitude) advantage in terms of the dynamic range of sensory response over the non-SAMul Py-DAPMA in buffer. In the presence of serum, both ligands can still detect heparin ratiometrically, however, the SAMul sensing mechanism of Py-G1 is switched off. Three series of SAMul dendrons based on L or D lysine and focal point hydrophobic groups, either pyrene or hydrocarbon chains, have been developed. Their ability to exhibit different chiral binding preferences towards chiral polyanions DNA and heparin have been studied. The way in which the ligands are displayed, which in turn depends on the nature of the hydrophobic component and the overall structural characteristics, are absolutely critical. Insertion of a simple linker allows expression of the chiral information at the nanoscale surface. The interaction between heparin and Mallard Blue (Mal-B) or a series of SAMul heparin binders are explored by NMR spectroscopy. The choice of buffer has significant impact on Mal-B/heparin binding, but precipitation of the Mal-B:heparin complex limits the opportunity for NMR analysis. NMR provides some insight to the binding events at the nanoscale and appears particularly useful for uncovering the role of ligands and dynamics in mediating binding with the best binder appearing to have best resolved ligand NMR resonances. The ability of C22-G1 and Py-G1 to ast as “nanoglue”, causing adhesion between polyanions and carbon nanotubes was studied. Both can self-assemble and bind to DNA and SWCNT respectively and C22-G1 is a better DNA and SWCNT binder. Although the attempt to quantitatively assay simultaneous DNA and SWCNT binding was unsuccessful, TEM imaging clearly allowed onto monitor the binding of DNA and CNT, and demonstrated that our synthetic nanoglue system causes them to co-assemble

Apoptosis in breast cancer cells

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Analysis of the flavonoid component of bioactive New Zealand mānuka (Leptospermum scoparium) honey and the isolation, characterisation and synthesis of an unusual pyrrole

The flavonoid components of New Zealand mānuka (Leptospermum scoparium) honey have been quantified in a series of 31 honeys of varying non-peroxide antibacterial activity to clarify discrepancies between previous studies reported in the literature. Total flavonoid content was 1.16 mg/100 g honey. The principal flavonoids present were pinobanksin, pinocembrin, luteolin and chrysin and together these represented 61% of the total flavonoid content. 1, 2-formyl-5-(2-methoxyphenyl)-pyrrole, which was weakly correlated with the non-peroxide antibacterial activity, was isolated from the flavonoid fraction and separately synthesised. 1 did not display inhibitory activity against Staphylococcus aureus in vitro and thus the origin of the correlation, which is still unknown, is not a direct contribution

Chiral recognition at self-assembled multivalent (SAMul) nanoscale interfaces – enantioselectivity in polyanion binding

Self-assembled multivalent (SAMul) ligands based on palmitic acid functionalised with cationic L/D-lysine bind polyanionic heparin or DNA with no chiral preference. Inserting a glycine spacer unit switches on chiral discrimination – a rare example of controlled chiral recognition at a SAMul nanoscale interface

Prevalence of metabolic syndrome and its associated factors among vegetarians in Malaysia

The prevalence and factors associated with metabolic syndrome (MetS) remain unknown in Malaysian vegetarians. This cross-sectional study aimed to determine the prevalence of MetS among vegetarians in Kuala Lumpur and Selangor and its associated factors. The data on socio-demographic characteristics, vegetarianism practises, lifestyle behaviours, body weight, height, waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and blood lipid profiles were collected from 273 vegetarians. A majority of the respondents were lacto-ovo vegetarians (44.0%), females (64.8%) and Chinese (54.9%). The prevalence of MetS was 24.2%. High BP (48.7%) and high WC (43.6%) were the most common MetS components. Females had lower WC, SBP, DBP, FBG, TG and higher HDL-c (p < 0.05) as compared to males. Multiple logistic regression analysis showed that being overweight and obese (Odds Ratio (OR) = 7.74, 95% Confidence Interval (CI): 4.04⁻14.82) was the main risk factor of MetS after being adjusted for sex and age. This study found that one in four vegetarians had MetS. An intervention programme should be developed to reduce Body Mass Index (BMI) among vegetarians, especially among those who are found to be overweight and obese

Surveillance of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) in high-rise apartment buildings in Selangor, Malaysia

Dengue is a mosquito-borne disease that causes high mortality and fatality rate among humans. The disease and the virus are spread through female Ae. aegypti and Ae. albopictus. 176 Modified Sticky Ovitraps (MSO) were installed in six blocks of high-rise apartment buildings in Petaling Jaya, Selangor. The specimens were collected throughout a duration of 26 weeks. NS1 dengue antigen kit was used to detect dengue antigen in mosquitoes, and positive mosquitoes were serotyped using Reverse Transcriptase-PCR, followed by Multiplex-PCR. The relationship between the number of Aedes mosquitoes and meteorological parameters was also determined. The association between the number of Aedes spp. captured, dengue cases, and positive specimens was also evaluated in this study. A total of 243 adult mosquitoes were successfully captured using MSO, with 95.1% (231) of the mosquitoes being Ae. aegypti, while 4.1% (10) and 0.8% (2) were Ae. albopictus and a mixed Aedes species, respectively. The molecular detection of the dengue virus showed that only 2 individual specimens of Ae. aegypti were positive, with one specimen being a dual serotype of DEN-II and IV, and another specimen was DENV-II. The weekly number of Aedes spp. captured correlated positively with Tmax, Tmin, and Tmean, and correlated negatively with RF and RH. The significant and useful data obtained from this study can be utilized in dengue vector management by local health authorities

Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD

BACKGROUND: We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone) before autologous stem cell transplantation (ASCT). Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone) or VTD (bortezomib/thalidomide/dexamethasone) induction, and analysed prognostic factors for outcome. PATIENTS AND METHODS: Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25), PAD (N = 31), VTD (N = 35)]. and received thalidomide maintenance for 2 years post-ASCT. RESULTS: 43 (47.3%) patients had International Staging System (ISS) III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS) and event-free (EFS) survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS. CONCLUSIONS: These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals