Abstract
Four series of 1,3-diaza-2-functionalized-adamantan-6-one derivatives, bearing at the 2 position SO, SO2, POCl and PO2H functional groups, were synthesized via a key quadruple Mannich reaction, followed by transformation of an aminal functionality into the final 2-thia- and 2-phospha compounds. The compounds were tested for cytotoxic activity against the mouse B16-F10 melanoma cell line. Malignant melanoma is notorious for its high resistance to chemotherapy, and new anti-melanoma drugs are urgently needed. The 2-thia compounds exhibited poor proliferation inhibition activity, but the 2-phospha derivatives showed significant activity, with IC50 values of 10-60 µM. The compounds induced cell death by G2/M cell cycle arrest, which led to apoptosis, as determined by Annexin V-FITC/PI staining, mitochondrial membrane potential changes assessed by the JC-1 reagent, caspases 3 and 7 activation, and morphological changes.
Keywords: Diaza-adamantane, melanoma, anticancer drugs, cytotoxicity, apoptosis, cell cycle.
Medicinal Chemistry
Title:Anti-Neoplastic Activity of 1,3-Diaza-2-Functionalized-Adamantan-6-One Compounds Against Melanoma Cells
Volume: 10 Issue: 1
Author(s): Yifat Sharabi-Ronen, Shlomo Levinger, Miri Ben-Dahan Lellouche and Amnon Albeck
Affiliation:
Keywords: Diaza-adamantane, melanoma, anticancer drugs, cytotoxicity, apoptosis, cell cycle.
Abstract: Four series of 1,3-diaza-2-functionalized-adamantan-6-one derivatives, bearing at the 2 position SO, SO2, POCl and PO2H functional groups, were synthesized via a key quadruple Mannich reaction, followed by transformation of an aminal functionality into the final 2-thia- and 2-phospha compounds. The compounds were tested for cytotoxic activity against the mouse B16-F10 melanoma cell line. Malignant melanoma is notorious for its high resistance to chemotherapy, and new anti-melanoma drugs are urgently needed. The 2-thia compounds exhibited poor proliferation inhibition activity, but the 2-phospha derivatives showed significant activity, with IC50 values of 10-60 µM. The compounds induced cell death by G2/M cell cycle arrest, which led to apoptosis, as determined by Annexin V-FITC/PI staining, mitochondrial membrane potential changes assessed by the JC-1 reagent, caspases 3 and 7 activation, and morphological changes.
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Cite this article as:
Sharabi-Ronen Yifat, Levinger Shlomo, Lellouche Ben-Dahan Miri and Albeck Amnon, Anti-Neoplastic Activity of 1,3-Diaza-2-Functionalized-Adamantan-6-One Compounds Against Melanoma Cells, Medicinal Chemistry 2014; 10 (1) . https://dx.doi.org/10.2174/15734064113099900002
DOI https://dx.doi.org/10.2174/15734064113099900002 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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