Synthesis and anti-proliferative activity evaluation of sorafenib derivatives with a 3-arylacryloyl hydrazide unit
Tóm tắt
A series of sorafenib derivatives with a 3-arylacryloyl hydrazide unit were designed and synthesized, and their anti-proliferative activity against human cancer cell lines (ACHN, HCT116, MDA-MB-231) were evaluated by MTT assay. Most of the synthesized compounds showed superior or similar cytotoxicity against the selected cell lines to the control sorafenib. Among these derivatives, compounds 8a, 8h, 8l, 8m, 11a and 11b showed potent anti-proliferative activity. Compounds 8h and 8m were selected for further evaluation of biological activity against more cancer cell lines. And oral administration of sorafenib analogue 8h at the same dose of sorafenib (30 mg/kg) in the pancreatic cancer Capan2 and Mia-PaCa2 xenograft models in nude mice showed tumour growth inhibition of 60.98 and 54.59 %, respectively, which is similar to the positive control sorafenib.
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