New Pyrano[2,3-d:6,5-d']dipyrimidine Derivatives-Synthesis, in vitro Cytotoxicity and Computational Studies

A new series of pyrano[2,3-d:6,5-d']dipyrimidine derivatives were synthesized and evaluated for their in vitro anticancer activity. The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR, 15N NMR, HR-MS and FT-IR spectral analyses. The cytotoxic activities of these compounds against four human cancer (HeLa, SKBR-3, HepG2, and Caco-2) cell lines were determined. The synthesized compounds showed high selectivity, and four compounds (5e, 5f, 5g and 5i) showed excellent potent cytotoxicity against HeLa, SKBR-3, and HepG2 cancer cell lines. Furthermore, four other compounds (5a, 5c, 5b and 5d) have exhibited significant cytotoxicity activity in the SKBR-3 and HepG2 cell lines respectively, with moderate cytotoxicity seen in the HeLa cell line. Additionally, a molecular docking study was conducted to predict the anti-cancer behavior of the synthesized compounds via inhibition of the allosteric site of Human Kinesin Eg5.