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Medicinal Chemistry
ISSN (Print): 1573-4064
ISSN (Online): 1875-6638
VOLUME: 10
ISSUE: 1
DOI: 10.2174/15734064113099900002









Anti-Neoplastic Activity of 1,3-Diaza-2-Functionalized-Adamantan-6-One Compounds Against Melanoma Cells

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Author(s): Yifat Sharabi-Ronen, Shlomo Levinger, Miri Ben-Dahan Lellouche and Amnon Albeck
Pages 27-37 (11)
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.
Affiliation:
Department of Chemistry, Bar Ilan University, Ramat Gan 52900, Israel.