Background: Chromene and anilinopyrimidine heterocyclics are attractive anticancer
compounds that have inspired many researchers to design novel derivatives bearing improved anticancer
Methods: A series of pyrimidine-fused benzo[f]chromene derivatives 6a-x were synthesized as
anticancer hybrids of 1H-benzo[f]chromenes and anilinopyrimidines. The inhibitory activity of the
synthesized compounds 6a-x against cell viability of human chronic myelogenous leukemia
(K562), human acute lymphoblastic leukemia (MOLT-4) and human breast adenocarcinoma
(MCF-7) cell lines was evaluated using MTT assay. The interaction of the most promising compound
with calf-thymus DNA was also studied using spectrometric titrations and Circular Dichroism
Results: Most compounds showed promising activity against tested cell lines. Among them, 2,4-
dimethoxyanilino derivative 6g exhibited the best profile of activity against tested cell lines
(IC50s = 1.6-6.1 μM) with no toxicity against NIH3T3 normal cell (IC50 >200 μM). The spectrometric
studies exhibited that compound 6g binds to DNA strongly and may change DNA conformation
significantly, presumably via a groove binding mechanism.
Conclusion: The results of this study suggest that the prototype compound 6g can be considered as
a novel lead compound for the design and discovery of novel anticancer agents.