Bioinspired computational design of lankacidin derivatives for improvement in antitumor activity.

The 17-membered polyketide, lankacidin C, exhibits considerable antitumor activity as a microtubule stabilizer by binding to the paclitaxel binding site. Esterification of the C-7/C-13 hydroxyl in lankacidin C was performed with acetyl, cinnamoyl and hydrocinnamoyl groups and their antitumor activity was assessed to improve the cytotoxicity of lankacidins through bioinspired computational design. Compared with the cytotoxicity of parent lankacidin C against the HeLa cell line, 13--cinnamoyl-lankacidin C demonstrated sevenfold higher cytotoxicity.

Ascitic Fluid Cytokines in Chronic Liver Disease: A Possible Prognostic Tool.

Introduction: Malignant ascites results from imbalance between protein in the peritoneal cavity and absorption of fluids via the lymphatic system. More than 20 interleukins (ILs) are known to play an important role in the protection against tumors.

Materials And Methods: Ascitic fluid IL-1B, IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ levels were assessed in 45 patients with liver cirrhosis and ascites as judged by histopathological and ultrasonographic findings.

Computational Prediction of the Mode of Binding of Antitumor Lankacidin C to Tubulin.

Lankacidin C, which is an antibiotic produced by the organism , shows considerable antitumor activity. The mechanism of its antitumor activity remained elusive for decades until it was recently shown to overstabilize microtubules by binding at the taxol binding site of tubulin, causing mitotic arrest followed by apoptosis. However, the exact binding mode of lankacidin C inside the tubulin binding pocket remains unknown, an issue that impedes proper structure-based design, modification, and optimization of the drug.