Synthesis and in vitro cytotoxicity of a homologous series of 5-halosubstituted $1,3-Bis(\omega-cyanoalkyl)$uracil analogues

A homologous series of twenty, hitherto unreported, analogues of 5-halosubstituted $1, 3-Bis(\omega-cyanoalkyl)uracil$acyclic nucleosides were synthesized by the series of alkylation reactions of 5-halouracils with the corresponding chloroacetonitrile, chloropropionitrile, chlorobutyronitrile and 5-chlorovaleronitrile $(Cl-(C_ 2)_n-CN: n=l, 2, 3, 4)\; in\; anhydrous\; DMSO\; (or DMF)/K_2CO_3(or NaH)\; under\; 75^{\circ}C$ temperature. Antitumor activities for the synthesized compounds were determined against three cell lines (FM-3A cell, P-388 cell and U-938 cell lines). The compounds that exhibited moderate activity to significant activity, included la-b, 2a-b, 3a-c, and 4a, whose compounds were active against P-388, FM-3A and U-937 cell lines with the compounds la, lb, and 2a, showing significant antitumor activity (inhibitory concentrations $(IC_{50})$ ranged from 2.2 to $7.0\mug/ml$). Their strucrure-activity relationship did not show any activity differences in their effective chain length (methyl, ethyl, propyl, butyl) in 1, 3-bis(.omega.-cyanoalkyl) uracils.