Oral Presentation Royal Australian Chemical Institute National Congress 2026

Synthesis and biological evaluation of dual neutron capture agent and PARP 1 inhibitors. (138170)

Georgia Lewis 1 , Nicholas Howell 2 , Chris Dobie 1 2 , Cloe Hildebrand 1 , Mitra Safavi-Naeini 2 , Danielle Skropeta 1
  1. School of Science, University of Wollongong, Wollongong, NSW, Australia
  2. Australian Nuclear Science and Technology Organisation (ANSTO), Lucas Heights, NSW, Australia

Poly ADP Ribose Polymerase 1 (PARP 1) is an abundant nuclear protein that has primary roles as a DNA damage sensor and signaller of repair.1 PARP 1 inhibitors are a targeted therapy used to suppress the DNA repair response of the PARP 1 enzyme, promoting cellular apoptosis.1 This is exacerbated in cells that have been treated with other DNA damage-inducing agents, such as chemotherapies.1 This strategy is currently utilised with several PARP 1 inhibitors approved by the Therapeutic Goods Administration for the treatment of primarily breast and ovarian cancers.2 In addition, PARP 1 inhibitors have also gained interest as potential radiotherapy sensitisers due to their involvement in DNA repair.3 Therefore, coupling PARP 1 inhibitors with radiotherapy treatment may prove effective at reducing radiation dosage administered to a patient while achieving the same therapeutic effect.

A new radiotherapy technique called Neutron Capture Enhanced Particle Therapy (NCEPT) is currently being developed at the Australian Nuclear Science and Technology Organisation (ANSTO). This therapy combines aspects of charged-particle and neutron capture therapy to elicit a more spatially targeted and enhanced radiotherapy dose.4,5  An area being developed alongside NCEPT is the production of novel neutron capture agents, which are small molecule drugs that deliver nuclei capable of neutron capture (e.g. the stable 10B isotope) to the primary tumour target site.5 This research explores the synthesis of novel boron-containing PARP 1 inhibitors and preliminary biological evaluations for their effectiveness as dual PARP 1 inhibitors and neutron capture agents.

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  5. Howell, N.; Middleton, R. J.; Sierro, F.; Wyatt, N. A.; Chacon, A.; Fraser, B. H.; Bambery, K. R.; Livio, E.; Dobie, C.; Bevitt, J. J.; Davies, J.; Dosseto, A.; Franklin, D. R.; Garbe, U.; Guatelli, S.; Hirayama, R.; Matsufuji, N.; Mohammadi, A.; Mutimer, K.; Rendina, L. M.; Rosenfeld, A. B.; Safavi-Naeini, M. Neutron Capture Enhances Dose and Reduces Cancer Cell Viability in and out of Beam during Helium and Carbon Ion Therapy. International Journal of Radiation Oncology, Biology, Physics 2024.