Biological Activity of Some Pyrimidine Derivatives: Cytotoxicity and Oxidative Stress Potential in Human Lung Cancer Cell line (A549).

Abstract

Compounds with pyrimidine ring in their structure have many biological activities including antimicrobial, antiviral and anticancer. Recently, studies related to their synthesis and so their applications have increased. In a previous study, a solid-phase microwave method was used to synthesized 25 new hydroxy- and methoxy-substituent 4,6-diarylpyrimidin-2 (1H) -ol and 4,6 diarylpyrimidin-2 (1H) –thiol compounds. In the present study, as a preliminary estimation of the anticancer activity, the cytotoxicity and oxidative stress induction potential of 6 derivatives that show highest antibacterial activities was evaluated in human lung epithelial cancer cell line (A549). Results of the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity test indicate that pyrimidine derivatives caused concentration-dependent cell death that IC50 values were calculated between 16.7 and 41.5 µg/mL. additonally, pyrimidine derivatives induced significant changes in malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activity; oxidative stress could be the mechanism of action of the tested pyrimidine derivatives in the cancerous cells. The results could be used to design the further in vivo and in vitro detailed studies to appreciate these pyrimidine derivatives anticancer activity, compare this activity with in-use known drugs, elucidate their mechanisms of action and estimate their safety.