epothilone-b and Neoplasms

Epothilones are a class of 16-membered macrolide compounds targeting microtubules. They have good anticancer activity and their mechanism of action is similar to that of paclitaxel. Epothilones are also highly active against cancer cells that are resistant to paclitaxel and other anticancer drugs. They have good water solubility, simple structure, and are relatively easy to totally synthesize and or semi-synthesize. These results immediately attracted great interest and research enthusiasm from pharmaceutical companies and academia. Herein, the various synthetic methods of epothilone B and its anticancer activity were summarized and analyzed.

Topics: Antineoplastic Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Epothilones; Humans; Molecular Structure; Neoplasms; Structure-Activity Relationship

Epothilones are the 16-membered macrolide compounds, exhibit microtubule-promoting activity, have the same anti-tumor mechanism as paclitaxel, and are expected to be the ideal substitutes for paclitaxel. However, natural epothilone compounds have been found to have disadvantages such as high toxicity in vivo, poor selectivity to tumor cells, and susceptibility to drug resistance. Herein, epothilone B was synthesized by fermentation, and it was galactosylated by chemical method. The toxicity in vitro of epothilone B and its galactosylated derivative was investigated by the MTT method. The anticancer activity evaluation in vitro was performed using a method similar to the antibody-directed enzyme-prodrug therapy (ADEPT) method. It indicated that the ratio of cytotoxicity between the free epothilone B and the galactosylated epothilone B was about 150. This would lay the foundation for the targeted treatment of cancer with epothilone glycosides.

Topics: Antineoplastic Agents; Cell Survival; Drug Screening Assays, Antitumor; Epothilones; Galactose; Humans; MCF-7 Cells; Microtubules; Neoplasms; Tubulin Modulators

Griseofulvin, an antifungal drug, has been shown in recent years to have anti-proliferative activities. We report here the synthesis of new analogs of griseofulvin, substituted in 2' by a sulfonyl group or in 3' by a sulfinyl or sulfonyl group. These compounds exhibit good anti-proliferative activities against SCC114 cells, an oral squamous carcinoma cell line showing pronounced centrosome amplification, and unexpected cytotoxic activities on HCC1937 cells, a triple negative breast cancer cell line resistant to microtubule inhibitors.

Topics: Cell Line, Tumor; Drug Resistance, Neoplasm; Griseofulvin; Humans; Neoplasms; Sulfones; Sulfoxides