Some 4H-benzo[h]chromene and 7H-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 4H-benzo[h]chromenes with modification at the 2-,3- positions and 7H-benzo[h]chromeno[2,3-d]pyrimidine at 2,3-positions. The structure–activity relationship (SAR) study revealed that the antitumor activity on 4H-benzo[h]chromene and 7H-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, 1H NMR, 13C NMR, 13C NMR-DEPT, and MS data.
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This research was supported by a program to support research and researchers at King Khalid University, Abha, Saudi Arabia and No. KKU-SCI-11-028. The authors deeply thank the Regional Center for Mycology & Biotechnology (RCMP), Al-Azhar University for carrying out the antitumor study, and Mr. Ali Y. A. Alshahrani for making the 1H NMR and 13C NMR spectra.
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El-Agrody, A.M., Fouda, A.M. & Al-Dies, AA.M. Studies on the synthesis, in vitro antitumor activity of 4H-benzo[h]chromene, 7H-benzo[h]chromene[2,3-d]pyrimidine derivatives and structure–activity relationships of the 2-,3- and 2,3-positions. Med Chem Res 23, 3187–3199 (2014). https://doi.org/10.1007/s00044-013-0904-x