Efficient Utilization of 6-Aminouracil to Synthesize Fused and Related Heterocyclic Compounds and Their Evaluation as Prostate Cytotoxic Agents with Cathepsin B Inhibition


6-aminouracil 1 was utilized to introduce different heterocyclic rings at C-6 position through various synthetic strategies. The synthesized compounds bear rings that are either directly attached to the uracil back bone as in compounds 6, 12a-c and 15, or attached through an amino bridge as compounds 3a-c, 5a, b, 7a, b, 9 and 10, or through an imino bridge as compound 18. Also, compounds 4, 8, 11a-c, 14, 16 and 17 bearing biologically active side chains were synthesized. In addition to, compounds 13, 19, 20, 21 and 22 bear fused rings to the uracil backbone. All synthesized compounds were evaluated for their anticancer activity against prostate PC3 cell line using in-vitro sulforhodamine-B (SRB) method, from which compounds 3a, c, 4, 5a, b, 6, 7a, b, 11a-c, 12a, b, 17 and 20 were the most active. These active compounds were further evaluated for their ability to inhibit cathepsin B enzyme by using enzyme-linked immunosorbent assay, which revealed that compounds 5a, b, 7a, 11a, 12a and 17 exhibited more than 50% inhibition of cathepsin B. Among which the phenyl thiourea derivative 17 was the most active exhibiting 82.3% inhibition, while the reference doxorubicin exerted 18.7% inhibition.

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Sarg, M. and El-Shaer, S. (2014) Efficient Utilization of 6-Aminouracil to Synthesize Fused and Related Heterocyclic Compounds and Their Evaluation as Prostate Cytotoxic Agents with Cathepsin B Inhibition. Open Journal of Medicinal Chemistry, 4, 39-60. doi: 10.4236/ojmc.2014.42003.

Conflicts of Interest

The authors declare no conflicts of interest.


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