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

Abstract

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.

Polysulfone nanofiltration membranes enriched with functionalized graphene oxide for dye removal from wastewater

“…This elucidated Structure 2 and supported the formation of an adduct structure ( Figure 2). 13 Nitrogen heterocyclic compounds are characterized by their high bioactivities as antibacterial [25,37], antiviral [26] and anticancer agents [30,36]. They compose robust hydrogen bonds with other compounds.…”

“…Much attention has been drawn to develop new approaches for synthesizing many categories of these heterocycles enriched with nitrogen [27,28]. Some of the multicomponent reactions to prepare pyrazolo-pyrido-pyrimidines depend on using amino pyrazole or amino-pyrimidine as starting materials with various catalysts [29][30][31].…”