Inhibitory effects of new 1,3-diethyl-8-mercapto xanthine derivatives in human MCF7 and K562 cancer cell lines

Author(s): HaiderN.Al-Sultani, RashaA.ghazal, AlaaM.Hayallah, LoayK.Abdulrahman, KhaledAbu- Hammour, ShathaAbu Hammad, MutasemO.Taha, MalekA.Zihlif

A series of new 2-methyl-2-[(1,3-Diethyl- 2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8- yl)thio]-N- substituted arylacetamides were synthesized by reacting the 8-merapto-xanthine derivative with appropriate prepared anilide. The structure of the newly prepared compounds were confirmed by 1HNMR, high resolutionmass spectrometer andmicroanalytical analysis. The antitumor activity of these compounds was evaluated on breast cancer (MCF7) and leukemic (K562) cell lines by cell viability assay utilizing the tetrazolium dye 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT). The result showed that some compounds illustrate different anti-tumor activitywhile others showed weak anti-tumor activity. For those with anti-tumor activity, the IC50 values range from 9.56-57 microM. Interestingly, compound para-nitro xanthine derivative showed the most encourag-ing activity against K562 leukemia cells and to a lesser extent againstMCf7 breast cancer cells. These findings indicate that the position and the type of the substitution on the phenylmoiety affect the activity of the xanthine derivatives and illustrate that the electron withdrawing groups increases the activity especially at the para position. The computer aid design approach revealed that the anti-tumor activity of these compoundsmay be attributable to their abilities to effectively bind and block oncogenic tyrosine kinases, particularly bcr/abl.

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