su-11248 and Liver-Neoplasms

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Traditional chemotherapy drugs are hard to reach a satisfactory therapeutic effect since advanced HCC is highly chemo-resistant. Sorafenib is an oral multikinase inhibitor that can suppress tumor cell proliferation, angiogenesis and induce cancer cell apoptosis. However, the poor solubility, rapid metabolism and low bioavailability of sorafenib greatly restricted its further clinical application. During the past decade, numerous sorafenib derivatives have been designed and synthesized to overcome its disadvantages and improve its clinical performance. This article focuses on the therapeutic effects and mechanisms of various sorafenib derivatives with modifications on the N-methylpicolinamide group, urea group, central aromatic ring or others. More importantly, this review summarizes the current status of the structure-activity relationship (SAR) of reported sorafenib derivatives, which can provide some detailed information of future directions for further structural modifications of sorafenib to discovery new anti-tumor drugs with improved clinical performance.

Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Proliferation; Chemistry, Pharmaceutical; ErbB Receptors; Humans; Liver Neoplasms; Molecular Structure; Protein Kinase Inhibitors; Sorafenib

A series of novel 4-thiazolidinone and indolin-2-one hybrid derivatives 5a-5s and 10a-10s have been designed and synthesized and their cytotoxic activities were evaluated in vitro against three human cancer cell lines including HT-29 (human colon cancer), H460 (human lung cancer), MDA-MB-231 (human breast cancer) by MTT assay. Several potent target compounds (5m, 5p, 5s, 10a, 10c-10g, 10m, 10p) were further evaluated against one cancer cell line SMMC-7721 (human liver cancer) and one normal cell line WI-38 (human fetal lung fibroblasts). Most of the prepared compounds exhibited significant antitumor activities against different human cancer cell lines. Compound 10c (IC(50) = 0.025 μM, 0.075 μM, 0.77 μM, 1.95 μM) was 52, 36, 4.8 and 3.3 times more active than Sunitinib (IC(50) = 1.3 μM, 2.7 μM, 3.7 μM, 6.47 μM) against HT-29, H460, MDA-MB-231 and SMMC-7721 cancer cell line, respectively.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Drug Design; Drug Screening Assays, Antitumor; Female; Fibroblasts; Humans; Indoles; Inhibitory Concentration 50; Liver Neoplasms; Lung Neoplasms; Pyrroles; Sunitinib; Thiazolidines