Cytotoxic and anticancer properties of some 4-aryl-3-arylcarbonyl-1-ethyl-4-piperidinols and related compounds

A previous investigation revealed that various 4-aryl-3-arylcarbonyl-1-ethy l-4-piperidinols and related vinylogs were cytotoxic to both murine and hum an tumour cell lines. In particular, 1a and 2a were identified as useful pr ototypic molecules. Structural modifications of 1a and 2a were accomplished leading to 1b-e and 2b-d which displayed cytotoxicity towards murine P388 and L1210 leukemic cells as well as human Molt 4/C8 and CEM T-lymphocytes. Among the new compounds, the greatest average potencies against these four cell lines were displayed by 1b and 2b, having approximately one quarter an d one half of the potency of the reference drug melphalan, respectively. Th e synthesis and bioevaluation of three open chain analogues of 1b-d, namely 3a-c, did not reveal unequivocally whether this molecular modification led to increases in cytotoxicity or not. Compounds 2a-d were substantially mor e active than melphalan using a panel of human tumour cell lines. In additi on, several compounds displayed selective toxicity to both colon and leukem ic cancer cells. The 4-piperidinol 2d was active in the in vivo hollow fibr e assay. This study revealed compounds with greater potency than 1a and 2a and it has confirmed that 1,3,4-trisubstituted-4-piperidinols and related c ompounds are novel groups of candidate antineoplastic and anticancer agents .