A series of bis[3,5-bis(benzylidene)-4-oxo-1-piperidinyl]amides 1 display potent cytotoxic properties towards a wide range of tumours. A number of the CC(50) and IC(50) values are in the range of 10(-8) M. Specifically, these compounds have the following important properties. First, greater toxicity was demonstrated towards certain tumours than various non-malignant cells. Second, various compounds in series 1 are toxic to a number of human colon cancer and leukaemic cells. Third, these compounds reverse P-gp mediated multidrug resistance. Various prototypic molecules such as 1a,b and 1i were identified as lead molecules for further studies. A representative lead molecule 1b induces apoptosis via internucleosomal DNA fragmentation and PARP cleavage in HSC-2 and HL-60 cells while flow cytometry revealed that this compound blocked the G2/M and S-phases in the cell cycle of human colon cancer HCT-116 cells.