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.