5-Cinnamoyl-6-aminouracil derivatives as novel anticancer agents. Synthesis, biological evaluation, and structure-activity relationships

Abstract

A biological evaluation in the series of 5-cinnamoyl-6-aminouracils has been undertaken. These compounds have been found to be in an extended planar conformation fitting well with a possible stacking interaction between the nucleic bases of DNA; thus an eventual anticancer activity by intercalation could be hoped. 1,3-Dimethyl-5-cinnamoyl-6-aminouracil was found to be active when administered ip against ip-implanted P388 leukemia in vivo (percent T/C = 124). Two other compounds, 1,3-dimethyl-5-cinnamoyl-6-[(2-morpholinoethyl)amino]uracil and 1,3-dimethyl-5-cinnamoyl-6-[(2-piperidinoethyl)amino]uracil, bearing a hydrophilic side chain on the 6-amino group, have exhibited cytoxic activity in vitro against L1210 leukemia. Structure-activity relationships have been determined from these results and from studies of biological interactions with DNA.

Synthesis, characterization and spectroscopic properties of some new phenylazo-6-aminouracil

“…For this purpose, the absorption spectra of phenylazo-6-aminouracil dyes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) were measured in various solvents at a concentration of approximately 10 -6 -10 -8 M and were run at different concentrations. The dyes were not fully dissolved, and any insoluble material in all solvents was filtered off.…”

“…5-Nitrouracil has been known to inhibit thymidine phosphorylase [9]. 5-Cinnamoyl-6-aminouracil derivatives have been investigated as anticancer agents [10]. Moreover, 6-Aminouracils found a wide application as starting materials for the synthesis of many fused uracils of biological significance, for example, pyrano-, pyrido-, pyrazolo-, pyrimido-, pyridazino-pyrimidines [11].…”

A study on tautomeric investigation of new hetarylazo-6-aminouracil

“…Generally, most of the substituted dyes have higher absorption maxima than their unsubstituted analogs. In the present study, spectral data for the various substituted hetarylazouracil dyes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) show that there is a general tendency for the visible absorption band to move bathochromically in accordance with the electron donor-acceptor groups in the diazo and coupling component. These involve a migration of electron density from the donor group toward the azo group.…”

“…The absorption spectra of hetaryl-azouracil dyes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were measured in various solvents at a concentration approximately 10 -6 -10 -8 M, run at different concentrations because of solubility problems ( Table 1). All the dyes have low solubility in chloroform which is the least polar solvent I used, and the absorption spectrum was only recorded in chloroform for dye 12.…”

“…10 Also, 5-cinnamoyl-6-aminouracil derivatives have been investigated as anticancer agents. 11 Moreover, 6-aminouracils find wide application as starting materials for the synthesis of many fused uracils of biological significance. 12 Therefore, uracils are very important for application in organic synthesis.…”