Diarylureas and Diarylamides with Pyrrolo[2,3-d]pyrimidine Scaffold as Broad-Spectrum Anticancer Agents
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概要
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A series of diarylureas and diarylamides possessing pyrrolo[2,3-d]pyrimidine scaffold was designed and synthesized. The in vitro antiproliferative activities of a selected group of the target compounds against NCI-60 cell line panel were tested and compared with Sorafenib and Imatinib as reference compounds. Most of the compounds showed strong and broad-spectrum antiproliferative activities. Compounds IVa, IVb, and IVd with benzamido moiety at position 4 of the pyrrolo[2,3-d]pyrimidine nucleus, para-disubstituted phenyl ring at N1-position of pyrrolo[2,3-d]pyrimidine scaffold, and urea linker showed strong and broad-spectrum anticancer results with high potencies and efficacies. In addition, the amide derivatives Vb and Vc demonstrated one-digit nanomolar IC50 values over two and one cell line(s), respectively. Amid all the target compounds, compound IVa demonstrated the best results in both one-dose and five-dose testing modes. It showed 109.18% mean % inhibition over the NCI-60 cancer cell line panel at 10 µ<span style="font-variant: small-caps;">M</span> concentration, submicromolar 50% inhibitory concentration (IC50) values over eight cell lines of eight different cancer types, and high efficacy with total growth inhibition (TGI) and 50% lethal concentration (LC50) values less than 4.22 µ<span style="font-variant: small-caps;">M</span> over three colon, ovarian, and prostate cancer cell lines. It showed superior potency and efficacy to Sorafenib and Imatinib over most of the tested cell lines.
著者
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Oh Chang-Hyun
Center for Biomaterials, Korea Institute of Science and Technology
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El-Gamal Mohammed
Center for Biomaterials, Korea Institute of Science and Technology
関連論文
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- Diarylureas and Diarylamides with Pyrrolo[2,3-d]pyrimidine Scaffold as Broad-Spectrum Anticancer Agents