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Updated: Oct 2, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Cytotoxic 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes and related compounds
Jonathan R Dimmock1, Amitabh Jha, Praveen Kumar
1College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan, Canada S7N 5C9. dimmock@skyway.usask.ca
Abstract:
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.
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