The benzosuberan ring system is an attractive scaffold for pharmaceutical scientists, combining aromatic and aliphatic properties in a rigid bicyclic structure system. This system offers some ten potential substitution sites and the ability to design, by substitution, a ‘perfect fit’ model generating high-affinity ligands targeted at a range of proteins to address several significant disease states including inflammatory conditions, central nervous system disorders and cancers, etc. There are a variety of elaborated benzocycloalkanone scaffolds in clinical use, amongst those are an integral part of some natural products such as Colchicines, Brussonol, Feveline, Bussealin-E and Theaflavin.1,2,3,4 A wide range of benzocycloalkanone derivatives have been developed5, with good bioactivities including anti-cancer, anti-inflammatory, anti-microbial, anti-estrogenic, anti-malarial, anti-pyretic, anti-ulcer, anti-tuberculosis, anti-obesity, anti-depressants, immunosuppressive and anti-platelet aggregation activities. The first stage of this project will be involved with novel molecule design followed by molecule synthesis, structure characterisation and purity analysis, etc. In the second stage of the project, the affinity of the novel compounds with the selected molecular targets will be examined by computational technique. Following the positive hits from the in silico screening, cancer cell lines will be selected and in vitro anti-cancer activity evaluation of these compounds will be performed.
1. Farghaly TA, Gomha SM, Dawood KM, Shaaban MR. Synthetic routes to benzosuberone-based fused- and spiro-heterocyclic ring systems. RSC Adv. 2016;6(22):17955-17979.
2. Crielaard BJ, van der Wal S, Lammers T, et al. A polymeric colchicinoid prodrug with reduced toxicity and improved efficacy for vascular disruption in cancer therapy. Int J Nanomedicine. 2011;6:2697-2703.
3. Terkeltaub RA. Colchicine update: 2008. Semin Arthritis Rheum. 2009;38(6):411-419.
4. Niel E, Scherrmann J-M. Colchicine today. Jt bone spine. 2006;73(6):672-678.
5. Barlow, J.W., Zhang, T., Woods, O., Byrne, A.J. and Walsh, J.J. (2011). Novel mast cell-stabilising amine derivatives of 3,4 dihydronaphthalen-1(2H)-one and 6,7,8,9-tetrahydro-5H-benzoannulen-5-one. Medicinal Chemistry, 7, 213-223.
Student requirements for this project A min. 2.1 (Hons) BSc in BSc in Medicinal Chemistry, Biological Sciences or related disciplines.
Self-Funded (Scholarship not available. Fees & Materials to be paid by the student. Materials costs not significant)
If you are interested in submitting an application for this project, please complete an Expression of Interest (www.dit.ie/media/documents/study/postgraduateresearch/EOI%20Form.doc) and email it to [email protected]