TY - JOUR
T1 - Anti-neoplastic activity of 1,3-diaza-2-functionalized-adamantan-6-one compounds against melanoma cells
AU - Sharabi-Ronen, Yifat
AU - Levinger, Shlomo
AU - Lellouche, Miri Ben Dahan
AU - Albeck, Amnon
PY - 2014/2
Y1 - 2014/2
N2 - 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 M. 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.
AB - 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 M. 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.
KW - Anticancer drugs
KW - Apoptosis
KW - Cell cycle
KW - Cytotoxicity
KW - Diaza-adamantane
KW - Melanoma
UR - http://www.scopus.com/inward/record.url?scp=84891350110&partnerID=8YFLogxK
U2 - 10.2174/15734064113099900002
DO - 10.2174/15734064113099900002
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C2 - 23627298
AN - SCOPUS:84891350110
SN - 1573-4064
VL - 10
SP - 27
EP - 37
JO - Medicinal Chemistry
JF - Medicinal Chemistry
IS - 1
ER -