Browsing by Author "Murnane, Robert"

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    A dissertation project for the forensic science laboratory. Birch reduction of ephedrine and analysis of by-products of forensic science interest
    (ACS, 2021-04-08) Herrmann, Kayleigh; Murnane, Robert; Brucoli, Federico
    This undergraduate dissertation project was designed to enhance organic and analytical chemistry skills of final year forensic science students. A modified Birch reaction method was employed to synthesize amphetamine from ephedrine and detect the most known byproduct of clandestine manufacture of amphetamines, e.g., 1-(1,4-cyclohexadienyl)-2-methylaminopropane (CMP). The use of this synthetic method led to simultaneous N-demethylation and dehydroxylation of the alkaloid. Harmful liquid ammonia and lithium metal, which are the typical reagents of the classic Birch reaction, were replaced by the safer sodium silica gel stage I (Na-SG-I) and an alcoholic proton source. Liquid chromatography–mass spectrometry (LC-MS) was used to monitor reaction progress and identify starting material, products, and byproducts, whereas proton and carbon nuclear magnetic resonance (1H and 13C NMR) and heteronuclear single-quantum correlation (HSQC) NMR spectroscopy experiments were employed to characterize amphetamine and the parent compound ephedrine. This multiweek project-based learning experience has been running for three years at De Montfort University (DMU), which offers a well-established Forensic Science BSc (Hons) undergraduate course. The students were guided with the help of an academic instructor through a research-like setting delving into synthesis, characterization, and analysis of a drug of abuse and its byproduct. As part of this learning experience, which culminated in a body of work that informed the content of final year dissertations, the students gained useful organic chemistry skills and consolidated previously acquired knowledge in trace analysis. A survey of the dissertations’ final grades and evaluation of end-of-project questionnaires revealed that students responded well to the challenges posed by the organic chemistry aspect of the lab and that the project topic and methods were engaging and very relevant to the forensic science course.
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    Synthesis and antitubercular activity of novel 4-arylalkyl substituted thio-, oxy- and sulfoxy-quinoline analogues targeting the cytochrome bc1 complex
    (Elsevier, 2023-06-05) Murnane, Robert; Brucoli, Federico; Tanna, Sangeeta; Allen, Renee; Santana-Gomez, Felipe; Parish, Tanya; Zloh, Mire
    A library of 4-substituted quinolines was synthesised based on the structural features of the privileged 4-(benzylthio)-6-methoxy-2-methylquinoline scaffold. Quinoline-based chemical probes have proven to be effective anti-tuberculosis agents with the ability of inhibiting components of Mycobacterium tuberculosis (MTB) respiratory chain including the b subunit of the cytochrome bc1 complex. Novel 4-(arylalkyl)-thio, -oxy and sulfoxy-quinoline analogues were tested for their ability to inhibit the growth of MTB H37Rv and QcrB mutant strains, and the compounds mode of action was investigated. Members of the 4-subtituted thio- and sulfoxyquinoline series exhibited significant growth inhibitory activity in the high nanomolar range against wild-type MTB and induced depletion of intracellular ATP. These probes also showed reduced potency in the QcrB T313I mutant strain, thus indicating the cytochrome bc1 oxidase complex as the molecular target. Interestingly, new 4-(quinolin-2-yl)oxy-quinoline 4i was more selective for the QcrB T313I strain compared to the wild-type strain.
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    Synthesis, Development and Biological Evaluation of Anti-tuberculosis Agents
    (De Montfort University, 2024-02) Murnane, Robert
    The aim of this research is to develop and synthesise anti-bacterial agents designed to combat the growing threat that bacterial anti-biotic resistance poses. The number of resistant strains of bacteria, such as Mycobacterium tuberculosis, has been growing over the last few decades. The rise in rifampicin resistant strains of M. tuberculosis poses a larger threat than other resistant strains of bacteria due to the landscape of M. tuberculosis treatment. In recent years, M. tuberculosis has been the second leading cause of death from infectious diseases, surpassing HIV/AIDs and second only to COVID-19, yet until recently very few new M. tuberculosis drugs had been approved since rifampicin in 1966. With rifampicin still being heavily relied on as a first line treatment around the world, it is paramount that new alternative treatments are developed to preserve the biological activity of rifampicin and to combat the growing cases of rifampicin resistant M. tuberculosis. To achieve this goal, several potential anti-tuberculosis agents, including novel cytochrome bc1 inhibitors, were synthesised and tested against both wild-type and resistant strains of M. tuberculosis. A number of hit-compounds bearing the quinoline scaffold exhibited anti-tuberculosis activity in vitro in the low-micromolar or high nanomolar range. Due to their favourable characteristics, these promising compounds might be developed into anti-bacterial candidates that can help alleviate the burden of antimicrobial resistance associated with the use of current antibiotics.