Communication
Organic & Biomolecular Chemistry
promising anti-proliferation activity against cancer cell models
in alignment with reported studies,9,10–12,17 providing infor-
mation on the role of substituent groups at the hydroxyl group
and potential biological targets of this natural product.
Furthermore, these chemical probes indicate that ergosterol
peroxide is a promising molecular scaffold as an early lead
compound for further therapeutic development against breast
cancer. Live cell imaging reveals significant co-localisation of
3m with endoplasmic reticulum fluorescent markers, while
the probe 3n with a longer linker between the borane core and
ergosterol peroxide showed accumulation in the mitochondria.
We demonstrate that chemical modifications can lead to
superior potency by causing accumulation in specific orga-
nelles to induce greater cellular damage. The identified poten-
tial targets warrant future validation studies via molecular
biology/chemical biology approaches.
4 C. Jiménez, E. Quiñoá, R. Rignera, R. Vilalta and
J. M. Quintela, J. Nat. Prod., 1989, 52, 619–622.
5 M. C. Deghrigue, L. Ghribi, M. V. D’auria, et al., J. Pharm.
Sci., 2014, 22, 64.
6 (a) W. Qing-Ping, X. Yi-Zhen, D. Zhaoqun, et al., PLoS One,
2012, 7, 44579; (b) D. B. Graca Sgarbi, A. J. Ribeiro-Silva,
I. Z. Carlos, C. L. Silva, J. Angluster and C. S. Alviano,
Mycopathologia, 1997, 139, 9–14.
7 (a) J. M. Gao, M. Wang, L. P. Liu, G. H. Wei, A. L. Zhang,
C. Draghici, et al., Phytomedicine, 2007, 14, 821–824;
(b) A. Ramos-Ligonio, A. López-Monteon and Á. Trigos,
Phytother. Res., 2012, 26, 938–943; (c) L. Ma, H. Chen,
P. Dong and X. Lu, Food Chem., 2013, 139, 503–508.
8 M. Kobori, M. Yoshida, M. Ohnishi-Kameyama and
H. Shinmoto, Br. J. Pharmacol., 2007, 150, 209–219.
9 N. Duarte, M. U. Ferreira, M. Martins, M. Viveiros and
L. Amaral, Phytother. Res., 2007, 21, 601–604.
10 (a) M. Bu, T. Cao, H. Li, M. Guo, B. B. Yang, C. Zeng and
L. Hu, ChemMedChem, 2017, 12, 466–474; (b) M. Bu,
T. Cao, H. Li, M. Guo, B. B. Yang, C. Zeng, Y. Zhou,
N. Zhang and L. Hu, Bioorg. Med. Chem. Lett., 2017, 27,
3856–3861; (c) G. Battogtokh, Y. S. Choi, D. S. Kang,
S. J. Park, M. S. Shim, K. M. Huh, Y.-Y. Cho, J.-Y. Lee,
H. S. Lee and H. C. Kang, Acta Pharm. Sin. B, 2018, 8, 862–
880.
Author contributions
M. M. M-M., T. L., and F. R. designed the study; T. L. per-
formed all the synthetic chemistry; and W. L. conducted cellu-
lar experiments with the support of F. R. All authors inter-
preted the data and reviewed and edited the manuscript. All
authors have approved the final version of the manuscript.
11 (a) I. J. Suarez-Arroyo, R. Rosario-Acevedo, A. Aguilar-Perez,
P. L. Clemente, L. A. Cubano, J. Serrano, R. J. Schneider
and M. M. Martínez-Montemayor, PLoS One, 2013, 8(2),
e57431; (b) M. M. Martínez-Montemayor, T. Ling,
I. J. Suárez-Arroyo, G. Ortiz Soto, C. S. Negrón,
M. Y. Lacourt-Ventura, A. Valentín-Acevedo, W. H. Lang
and F. Rivas, Front. Pharmacol., 2019, 10, 115.
Conflicts of interest
The authors declare that they have no competing interest.
12 I. Fernandez and A. Robert, Org. Biomol. Chem., 2011, 9,
4098–4107.
Acknowledgements
This study was supported by ALSAC St Jude Children’s 13 M. Axelrod, V. L. Gordon, M. Conaway, A. Tarcsafalvi,
Research Hospital (F. R.) and NIH/NIGMS SC3GM111171
Universidad Central del Caribe School of Medicine
D. J. Neitzke, D. Gioeli and M. J. Weber, Oncotarget, 2013,
4, 622–635.
(M. M. M-M). We thank the following core facilities for techni- 14 S. M. Mense and L. Zhang, Cell Res., 2006, 16, 681–692.
cal assistance: Analytical Technologies, Flow Cytometry and 15 D. Chiabrando, F. Vinchi, V. Fiorito, S. Mercurio and
Cell Sorting, Cell and Tissue Imaging Core, Center for
E. Tolosano, Front. Pharmacol., 2014, 5, 1–24.
Proteomics and Metabolomics, and Bioinformatics core 16 (a) R. Chiorean, C. Braicu and I. Berindan-Neagoe, Breast,
(Dr David Finkelstein), which are all supported fully or in part
by ALSAC and Cancer Center Support Grant P30CA021765
from the National Cancer Institute.
2013, 22, 1026–1033; (b) K. J. Chavez, V. Sireesha,
S. V. Garimella and S. Lipkowitz, Breast Dis., 2010, 32, 35–
48; (c) W. D. Foulkes, I. E. Smith and J. S. Reis-Filho, N.
Engl. J. Med., 2010, 363, 1938–1948.
17 H. Y. Wu, F. L. Yang, L. H. Li, Y. K. Rao, T. C. Ju,
W. T. Wong, C. Y. Hsieh, M. V. Pivkin, K. F. Hua and
S. H. Wu, Sci. Rep., 2018, 8, 17956.
Notes and references
1 T. Nakanishi, H. Murata, Y. Inatomi, A. Inada, J. Murata, F. 18 Z. Zhang, L. Zhang, L. Zhou, Y. Lei, Y. Zhang
A. Lang, K. Yamasaki, M. Nakano, T. Kawahata, H. Mori
and C. Huang, Redox Biol., 2018, DOI: 10.1016/
and T. Otake, Natural Medicines, 1998, 52, 521–526.
j.redox.2018.11.005.
2 K. Yasukawa, T. Akihisa, H. Kanno, T. Kaminaga, 19 C. Florean, S. Song, M. Dicato and M. Diederich, Free
M. Izumida, T. Tamura and M. Takido, Biol. Pharm. Bull.,
1996, 19, 573–576.
3 Y. Takahashi, M. Uda, T. Ohashi, K. Nakano, K. Murakami
and T. Tomimatso, Phytochemistry, 1991, 30, 4117–4120.
Radical Biol. Med., 2019, 134, 177–189.
20 (a) H. M. Schipper, S. Cissé and P. A. Walton, Exp. Cell Res.,
1993, 207, 62–67; (b) Y. Han, M. Li, F. Qiu, M. Zhang and
Y. H. Zhang, Nat. Commun., 2017, 8, 1307.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2019