From the recent studies, 3,5-dibenzoyl-1,4-dihydropyridone (DHP) derivatives, DP-7, has emerged as a potent multidrug reverting agent that inhibits efflux of drug from cell wall by inhibiting the activity of ATP Binding Cassettes. On the other hand, dihydropyrimidine (DHPM) derivative, (aza analogue) namely, monastrol inhibits the protein Eg5, which is responsible for the separation of daughter chromosomes during cell division and controls the growth of the tumor cells. In the present report, we have reported the hybridize molecules of these two potent molecules to check the dual action in cancer chemotherapy by synthesizing various thio and oxo analogues, bearing substituted aryl groups at 4th position of the DHPM ring. The newly synthesized molecules were screened for antiproliferative effects in mdr1-gene transfected mouse lymphoma cell line (l5178 y). Among these newly synthesized compounds namely, IIh, Ig, Ii, and Ij showed a very potent antiproliferative activity.