Uche, FI, McCullagh, J, Claridge, T, Richardson, A and Li, W (2018) Synthesis of (aminoalkyl)cycleanine analogues: cytotoxicity, cellular uptake, and apoptosis induction in ovarian cancer cells. Bioorganic and Medicinal Chemistry Letters, 28 (9). pp. 1652-1656. ISSN 1464-3405

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Our previous studies demonstrated that cycleanine, a macrocyclic bisbenzylisoquinoline (BBIQ) alkaloid, showed potent anti-ovarian cancer activity via apoptosis induction. Here, we synthesized two novel (aminoalkyl) cycleanine analogues (2 and 3) through a simple and efficient two-step reaction starting from cycleanine isolated from Triclisia subcordata Oliv. These analogues showed greater potency than the unmodified cycleanine in three human ovarian cancer cell lines. Both 2 and 3 induced apoptosis in ovarian cancer cells by activations of caspases 3/7, cleavage of PARP, increase in subG1 cell cycle phase and in the percentage of apoptotic cells. Further confocal fluorescence microscopy analysis confirmed the cellular uptake of alkaloids in ovarian cancer cells by using the unique (alkynyl)cycleanine (3) via click chemistry reaction. Our results suggest that cycleanine could be a hit compound for the future development in attacking ovarian cancer.

Item Type: Article
Uncontrolled Keywords: Cycleanine; Bisbenzylisoquinoline alkaloid; Ovarian cancer; Semi-synthesis; Cellular uptake; Apoptosis
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 15 Mar 2018 11:48
Last Modified: 16 Mar 2019 01:30
URI: https://eprints.keele.ac.uk/id/eprint/4575

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