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Synthesis and study of pyrimidine-phthalimide hybrids as VEGFR2 inhibitors with antiproliferative activity. | LitMetric
Thalidomide, a once notorious sedative, is now clinically used as an antitumor agent. We aimed to use it as a lead compound for designing pyrimidine-phthalimide hybrids. Nucleophilic substitution reaction of thalidomide analog with primary and/or secondary aliphatic amines afforded pyrimidine-phthalimide hybrids , and . Compound showed high antiproliferative activity against four cell lines: HepG-2 (IC: 7.86 ± 0.5 μM), MCF-7 (IC: 2.77 ± 0.1 μM), HCT-116 (IC: 5.73 ± 0.4 μM) and PC-3 (IC: 8.32 ± 0.5 μM), with selective cytotoxicity for WI-38 (IC: 43.2 ± 2.56 μM). arrested MCF-7 cells at S phase of the cell cycle and increased the total apoptotic cells by 50-fold. inhibited VEGFR2 (IC: 0.130 ± 0.02 μM). was capable of binding at the VEGFR2 binding site, forming hydrogen bond interactions with Asp1046 and Glu885 in a similar way to sorafenib.
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Port Said University , Port Said, 42511, Egypt.
Thalidomide, a once notorious sedative, is now clinically used as an antitumor agent. We aimed to use it as a lead compound for designing pyrimidine-phthalimide hybrids. Nucleophilic substitution reaction of thalidomide analog with primary and/or secondary aliphatic amines afforded pyrimidine-phthalimide hybrids , and .
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