- BSc (Hons), Chemistry. University of Canterbury, 1996
- PhD, Synthetic Organic Chemistry. University of Canterbury, 2003
Background and role at Cawthron
Darby is a synthetic organic/medicinal chemist who joined the Cawthron in 2013, as a member of the Research and Development team. He was previously a Research Fellow at the Auckland Cancer Society Research Centre, one of the world's leading anti-cancer drug development laboratories, where he worked for over ten years across a wide range of projects, often in collaboration with international commercial or academic groups.
During his PhD, he developed the first total synthesis of hydroxystrobilurin A (a member of the strobilurin family of fungicidal natural products, which are produced by a variety of fungal species worldwide), based on the utilization of palladium-catalyzed carbon-carbon bond-forming methodologies.
His drug development experience includes the elaboration of hits from high-throughput screens of small-molecule chemical libraries into sets of analogues, to explore the structure-activity relationships around leads and generate more biologically active and drug-like candidates. He has also worked as a freelance editor of scientific manuscripts, prior to their being submitted for publication.
Darby is particularly interested in the synthesis and semi-synthesis of biologically active molecules, including in the development of natural-product based compounds as possible treatments for disease, and in the use of novel chemical reagents and structural units in this process.
Technical skills, experience and interests
- synthetic organic chemistry, medicinal chemistry
- total synthesis and semi-synthesis of natural products and analogues
- drug development
- NMR spectroscopy
- scientific writing/editing
- Field JJ, Kanakkanthara A, Brooke DG, Sinha S, Pillai SD, Denny WA, Butt AJ and Miller JH 2016. Microtubule-stabilizing properties of the avocado-derived toxins (+)-(R)-persin and (+)-(R)-tetrahydropersin in cancer cells, and activity of related synthetic analogs. Investigational New Drugs. June 2016, Volume 34, Issue 3, pages 277–289.
- Yin YD, Brooke DG, Heinrich DM, Denny WA and Jamieson SMF 2014. The activity of SN33638, an inhibitor of AKR1C3, on testosterone and 17β-estradiol production and function in castration-resistant prostate cancer and ER-positive breast cancer. Oncol. 4:159.
- Flanagan JU, Atwell GJ, Heinrich DM, Brooke DG, Silva S, Rigoreau LJM, Trivier E, Turnbull AP, Raynham T, Jamieson SMF and Denny WA 2014. Morpholylureas are a new class of potent and selective inhibitors of the type 5 17-β-hydroxysteroid dehydrogenase (AKR1C3). Bioorganic & Medicinal Chemistry. Volume 22, Issue 3. Pages 967–977 .
- Brooke DG, van Dam EM, Watts CKW, Khoury A, Dziadek MA, Brooks H, Graham LK, Flanagan JU and Denny WA 2014. Targeting the Warburg effect in cancer: relationships for 2-arylpyridazinones as inhibitors of the key glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3). Bioorganic & Medicinal Chemistry. Volume 22, Issue 3. Pages 1029–1039 .
- Gamage SA, Brooke DG, Redkar S, Datta J, Jacob ST and Denny WA 2013. Structure-activity relationships for 4-anilinoquinoline derivatives as inhibitors of the DNA methyltransferase enzyme DNMT1 . Bioorganic & Medicinal Chemistry. Volume 21, Issue 11. Pages 3147–3153 .
- Jamieson SMF, Brooke DG, Heinrich D, Atwell GJ, Silva S, Hamilton EJ, Turnbull AP, Rigoreau LJM, Trivier E, Soudy C, Samlal SS, Owen PJ, Schroeder E, Raynham T, Flanagan JU and Denny WA 2012. 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids: Highly potent and selective inhibitors of the type 5 17-β-Hydroxysteroid Dehydrogenase AKR1C3 . J. Med. Chem 2012, Volume 55, Issue 17. Pages 7746–7758.
- Brooke DG, Shelley EJ, Roberts CG, Denny WA, Sutherland RL and Butt AJ 2011. Synthesis and in vitro evaluation of analogues of avocado-produced toxin (+)-(R)-persin in human breast cancer cells. Bioorganic & Medicinal Chemistry, Volume 19, Issue 23. Pages 7033–7043.
- Phiasivongsa P, Redkar SG, Gamage S, Brooke DG, Denny W, Bearss DJ and Vankayalapati H 2010. Quinoline derivatives for modulating DNA methylation . US Patent 7,790,746 2010.
- Datta J, Ghoshal K, Denny WA, Gamage SA, Brooke DG, Phiasivongsa P, Redkar S and Samson TJ 2009. A new class of Quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA Methyltransferase 1 activity and inducing its degradation. Cancer Research, Issue 69; Page 4277.
- Brooke DG and Morris JC 2008. Total synthesis of hydroxystrobilurin A via Stille coupling. Tetrahedron Letters. Volume 49, Issue 15. Pages 2414–2417 .