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Title: Chemical and biological studies on natural and synthetic Novel Psychoactive Substances
Author: Arunotayanun, W.
ISNI:       0000 0004 5362 6699
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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Over the past decade, the availability of novel psychoactive substances (NPS), so called “legal highs”, has been increasing dramatically worldwide. Natural products (NP) and synthetic compounds based on NP are amongst the most commonly offered by online vendors. Most synthetic substances have recently been introduced and very little is known about their chemical and biological properties. In this project, 18 novel synthetic NPS were selected and purchased online. The full chemical characterizations using NMR, ESI-MS, HRMS, IR and UV techniques as well as in vitro neurological assays were carried out. The chemical analysis of these compounds provided a complete set of fundamental information for future analytical, forensic and synthetic work whereas the neurological results from this study made several noteworthy contributions on pharmacological and toxicological studies. One of the most valuable findings to emerge from this study is that some substances of interest including STS-135, QUPIC, 5F-QUPIC, QUCHIC, AMT, 5-MeO-DALT, 5-EAPB, 3,4-CTMP and 4-MeO-PCP, were found to exhibit moderate to high affinity interactions to at least one neurotransmitter and receptor associated with psychoactive activity suggesting that these products had a powerful potential to generate psychedelic effects in users. Moreover, some of these substances namely 5-MeO-DALT, 5-EAPB, 3,4-CTMP, 5-MAPB and MTTA, could lead to serious adverse reactions in users as they showed appreciable affinity to the 5-HT2B receptor which is known to be associated with valvular heart diseases after long term use. Another striking finding from this study was the antibacterial activities of three related isomers isolated from a commercial sample of LY-2183240, an NPS in the cannabinoid class. A 2,5-regioisomer of LY-2183240 and a novel compound, the 5,1 isomer of LY-2183240, exhibited remarkable antibacterial activities while LY-2183240 (1,5-regioisomer) was found to possess fair activity against the tested S. aureus strains, despite the fact that the structures of these three compounds were closely related. Appreciable activities were also observed for MTTA against S. aureus, as well as 5-MeO-DALT against E. coli. For natural product NPS, whilst some are well-known, without any regulation, these materials are often of dubious identity or are adulterated with other psychoactive plants or compounds, which could cause serious harm to users. Therefore, in this research, a metabolomic approach combined with multivariate data analysis was applied to examine all the metabolites present in the four top natural product NPS (Kratom, Cacti, Fly Agaric, and Hawaiian Baby Woodrose) from various UK websites. The sample preparation, data bucketing and data analysis were developed and 1H-NMR spectroscopy was selected as a tool for sample analysis due to several advantages over other methods. An interesting finding to emerge from this study was the detection of two adulterants in the kratom sample, which were identified by a metabolomic study to possess a distinct metabolite profile compared to the rest of the kratom products. These adulterants were isolated and confirmed as oxoglaucine and glaucine which have recently been classified as NPS. This clearly suggested the practical application of 1H-NMR metabolomic technique as a rapid and efficient analytical tool to produce a valuable database for the quality control of natural product NPS and for the identification of adulterants in the future.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available