<p> This thesis describes the isolation and structural determination of flavonoids from the
heart wood of Prunus avium as well as synthesis of polyhydroxy pyrrolidine derivatives and aniline core structures as potential antibacterial agents. Nitrogen-synthons containing
saturated heterocyclic systems and aniline core structures are important synthons in
organic chemistry because of their presence in many biologically-active natural products.
Mycobacterial viability is dependent upon the ability of the organism to produce an intact cell wall. Therefore, compounds that interfere with the biosynthesis of the cell wall complex glycons have the potential to become new drugs for the treatment of mycobacterial infections. The oligosaccharide galactan is one of the major structural components of the outer wall of the micro-organism. Galactofuranose is essential for cell growth and survival and therefore, its biosynthesis constitutes a new drug target. The biosynthetic process involves several enzymes having Uridine-diphosphogalacto furanose (UDP-Galf) as the substrate; uridine 5^1 -diphosphogalacto pyranose mutase which catalyzes the interconversion of UDP galacatopyranose to UDP-galactofuranose as well as Galf-transferase. We are seeking and designing molecules that could be mechanistic probes and/or inhibitors of efflux pumps to potentially combat multidrug resistance.</p> <p> The isolation and structure-determination of six naturally occurring Flavan-type Natural products was performed. Such derivatives are known to reverse multiple-drug-resistance (MDR) in persistent microbial infections. The synthesis of pyrrolidine-based antibacterial agents was attempted using two different approaches from tartaric acid. These derivatives were designed as potential transition-state mimics of a carbohydrate processing enzyme specific to TB. A synthetic approach to the aromatic core structure of the antibacterial agent Platensimycin was also investigated. The synergistic use of cytotoxic agents in conjunction with efflux-pump modulators is an
emerging area of research in the MDR field; our efforts to make available materials for high-throughput screening in this area will be described.</p> / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/21550 |
| Date | 01 1900 |
| Creators | Bollareddy, Endreddy |
| Contributors | McNulty, James, Chemistry |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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