Journal article
Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere
BA Chalmers, H Xing, S Houston, C Clark, S Ghassabian, A Kuo, B Cao, A Reitsma, CEP Murray, JE Stok, GM Boyle, CJ Pierce, SW Littler, DA Winkler, PV Bernhardt, C Pasay, JJ De Voss, J McCarthy, PG Parsons, GH Walter Show all
Angewandte Chemie International Edition | WILEY-V C H VERLAG GMBH | Published : 2016
Abstract
Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity,..
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Awarded by Australian Research Council
Funding Acknowledgements
This work was supported by the Australian Research Council (Future Fellowship to C.M.W., FT110100851), the University of Queensland, the CSIRO (Melbourne), NCRIS 2013 THD grant funding to the TIA-QLD Node from Therapeutic Innovation Australia (TIA), and infrastructure purchased using investment funds from the Queensland Government Smart State Research Facilities Fund as well as from Therapeutic Innovation Australia. We sincerely thank Michael Falkiner (CSIRO) for the supply of dimethylcubane-1,4-dicarboxylate. Furthermore, we acknowledge Dani Cardozo (CSIRO) for assistance with the SAHA-related animal work and Prof. Anders Woetmann (University of Copenhagen) for kindly supplying the MyLa2059 cell line. Dr. Greg Daglish (Department of Agriculture and Fisheries) kindly provided the Tribolium castaneum material for use in tests. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government.