Photoactivated cell-killing involving a low molecular weight, donor-acceptor diphenylacetylene

Chisholm, David R. and Lamb, Rebecca and Pallett, Tommy and Affleck, Valerie and Holden, Claire and Marrison, Joanne and O'Toole, Peter and Ashton, Peter D. and Newling, Katherine and Steffen, Andreas and Nelson, Amanda K. and Mahler, Christoph and Valentine, Roy and Blacker, Thomas S. and Bain, Angus J. and Girkin, John and Marder, Todd B. and Whiting, Andrew and Ambler, Carrie A. (2019) Photoactivated cell-killing involving a low molecular weight, donor-acceptor diphenylacetylene. Chemical Science, 10 (17). pp. 4673-4683. ISSN 2041-6520

Text (Photoactivated_cell_killing_involving_a_low_molecular_weight_donor_acceptor_diphenylacetylene)
Photoactivated_cell_killing_involving_a_low_molecular_weight_donor_acceptor_diphenylacetylene.pdf - Published Version
Available under License Creative Commons Attribution-NonCommercial-NoDerivs.
Download (3MB)

Abstract

Photoactivation of photosensitisers can be utilised to elicit the production of ROS, for potential therapeutic applications, including the destruction of diseased tissues and tumours. A novel class of photosensitiser, exemplified by DC324, has been designed possessing a modular, low molecular weight and ‘drug-like’ structure which is bioavailable and can be photoactivated by UV-A/405 nm or corresponding two-photon absorption of near-IR (800 nm) light, resulting in powerful cytotoxic activity, ostensibly through the production of ROS in a cellular environment. A variety of in vitro cellular assays confirmed ROS formation and in vivo cytotoxic activity was exemplified via irradiation and subsequent targeted destruction of specific areas of a zebrafish embryo.