Abstract
Some 4
H
-benzo[
h
]chromene and 7
H
-benzo[
h
]chromeno[2,3-
d
]pyrimidine derivatives were prepared as potential cytotoxic agents. The in vitro cytotoxic activity of the synthesized compounds was investigated in comparison with the well-known anticancer standard drugs Vinblastine, Colchicine, and Doxorubicin using MTT colorimetric assay. It was found that compounds
23
,
15
,
20
, and
21
showed the highest anticancer activity against the three tumor cell lines MCF-7, HCT, and HepG-2, compared with Vinblastine and Colchicine, while compound
23
was the most active against HepG-2 as compared with Doxorubicin. We explored the SAR of 4
H
-benzo[
h
]chromenes with modification at the 2-,3- positions and 7
H
-benzo[
h
]chromeno[2,3-
d
]pyrimidine at 2,3-positions. The structure
–
activity relationship (SAR) study revealed that the antitumor activity on 4
H
-benzo[
h
]chromene and 7
H
-benzo[
h
]chromeno[2,3-
d
]pyrimidine derivatives were significantly affected by the lipophilicity (hydrophobic or hydrophilic), of the substituent at 2-,3- and 2,3-positions. Structures of these compounds were established on the basis of spectral data, IR,
1
H NMR,
13
C NMR,
13
C NMR-DEPT, and MS data.