Open AccessSynthesis, Characterization and Docking Study of Novel Pyrimidine Derivatives as Anticancer Agents
Author(s) -
Manal El-Saidi,
Ahmed A. ElSayed,
Erik B. Pedersen,
Mohamed A. Tantawy,
Nadia A. Mohamed,
W. A. Gad
Publication year - 2020
Publication title -
indonesian journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.273
H-Index - 14
eISSN - 2460-1578
pISSN - 1411-9420
DOI - 10.22146/ijc.50582
Subject(s) - chemistry , pyrimidine , thiourea , docking (animal) , guanine , stereochemistry , dna , dna replication , thiouracil , hydrogen bond , cyclin dependent kinase , cell cycle , combinatorial chemistry , apoptosis , biochemistry , molecule , organic chemistry , medicine , nucleotide , nursing , thyroid , gene
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.