Cytotoxic 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes and related compounds
Dimmock, Jonathan R × Jha, Amitabh Kumar, Praveen Zello, Gordon A Quail, J Wilson Oloo, Eliud O Oucharek, Jennifer J Pasha, Mohammed K Seitz, Dallas Sharma, Rajendra K Allen, Theresa M Santos, Cheryl L Manavathu, Elias K De Clercq, Erik Balzarini, Jan Stables, James P #
European journal of medicinal chemistry vol:37 issue:1 pages:35-44
A series of 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes 2a-c and 4 and a related acyclic analogue 6a were synthesised and converted to the corresponding Mannich bases 3a-c, 5 and 6b. Evaluation of these compounds against murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed that the Mannich bases were more cytotoxic than the corresponding unsaturated ketones. 1,4-bis(3-Dimethylaminomethyl-2-oxo-1-cyclohexylmethylene)benzene dihydrochloride (3a) had lower IC(50) values than melphalan against the four cell lines and was 15 times more potent than this drug when examined against a panel of human tumours.