Synthesis, Characterization and Docking Study of Novel Pyrimidine Derivatives as Anticancer Agents

Manal Mohamed Talaat El-Saidi(1), Ahmed Ali El-Sayed(2*), Erik Bjerregaard Pedersen(3), Mohamed Abdelhamid Tantawy(4), Nadia Ragab Mohamed(5), Wafaa Ahmed Gad(6)

(1) Photochemistry Department, Chemical Research Division, National Research Center, Dokki, Giza, 12622, Egypt
(2) Photochemistry Department, Chemical Research Division, National Research Center, Dokki, Giza, 12622, Egypt
(3) Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
(4) Hormones Department, Medical Research Division, National Research Center, Dokki, Giza, 12622, Egypt
(5) Photochemistry Department, Chemical Research Division, National Research Center, Dokki, Giza, 12622, Egypt
(6) Photochemistry Department, Chemical Research Division, National Research Center, Dokki, Giza, 12622, Egypt
(*) Corresponding Author


New compounds 5 and 9 using DNA bases e.g. Adenine 1 and Guanine 6 derivatives have been synthesized. The use of simple methods to synthesize compounds 5 and 9 were done using pyrimidine as an alternative DNA base ring. Another design to synthesize new simple pyrimidine rings utilizing thiourea and ethylcyano acetate to afford 6-amino-2-thiouracil was adopted. The reaction of thiouracil 10 with chloro cyano or chloro ester and ketone, resulted in the formation of adduct compounds 18-21, rather than the formation of compound 17. All the synthesized compounds were subjected to docking study, in order to gain insights into their binding modes against cyclin-dependent protein kinase 2 (CDK-2) that is involved heavily in cell cycle regulation and receptor protein B-cell lymphoma 2 (BCL-2) which is involved in cell apoptosis. These targets were selected based on their key roles in cancer progression via the regulation of the cell cycle and DNA replication. Molecular-docking analyses showed that compound 14e was the best docked ligand against both targets, as it displayed the lowest binding energy, critical hydrogen bonds and hydrophobic interactions with the targets.


DNA; guanidine; adenine; 6-aminothiouracil; hydrazonoyl halides; thiadiazole; phenylisocyanate; molecular docking

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