Add time:07/30/2019 Source:sciencedirect.com
The increasing interest on new drug discovery is constantly up to date as drugs do not increase survival adequately against increasing cancer cases worldwide. Based on the reported anticancer activity of coumarin, chalcone and urea derivatives, the present investigation dealt with the design and synthesis of coumarin derivatives bearing diversely substituted chalcone-urea moieties 5a-k. Through a structure-based molecular hybridization approach, a series of novel coumarin-chalcone derivatives containing urea moiety was synthesized and screened for their in vitro antiproliferative activities against the cancer cell lines (H4IIE and HepG2). In addition, the synthesized compounds were tested on a cell line that was not cancerous (CHO) and the damage, it could give to normal cells was determined. Among the synthesized compounds, 5k exhibited better inhibition of H4IIE compared to Sorafenib. 5j also showed better inhibition against HepG2 than Sorafenib. In particular, 5k induced H4IIE apoptosis, arrested cell cycle at the S phase. Therefore, 5k and 5j may be potent antitumor agents, representing a promising lead for further optimization.
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