title: Anti-neoplastic activity of 1,3-diaza-2-functionalized-adamantan-6-one compounds against melanoma cells.
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.
authors.forename: Yifat
authors.initials: Y
authors.lastname: Sharabi-Ronen
authors.forename: Shlomo
authors.initials: S
authors.lastname: Levinger
authors.forename: Miri Ben-Dahan
authors.initials: MB
authors.lastname: Lellouche
authors.affiliation: Department of Chemistry, Bar Ilan University, Ramat Gan 52900, Israel. amnon.albeck@biu.ac.il.
authors.forename: Amnon
authors.initials: A
authors.lastname: Albeck
mesh_terms: D000218:Adamantane / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D015394:Molecular Structure; D013424:Sulfanilamides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001372:Aza Compounds; D013424:Sulfanilamides; D000218:Adamantane