Design, synthesis, and biological evaluation of novel artemisinin-based HDAC inhibitors with antitumor and antimalarial activities.

In addition to the clinical applications as antimalarial agents, artemisinin and its derivatives have demonstrated significant potential in antitumor drug discovery. To enhance antitumor activity, a novel series of artemisinin-containing histone deacetylase (HDAC) inhibitors was designed using a hybrid strategy that fused the artemisinin moiety with HDAC inhibitory functionality. A triazole ring was incorporated into the linker region to improve water solubility.

Discovery of Novel p53-MDM2 Inhibitor (RG7388)-Conjugated Platinum Complexes as Potent Antitumor Agents.

While a number of p53-MDM2 inhibitors have progressed into clinical trials for the treatment of cancer, their progression has been hampered by a variety of problems, including acquired drug resistance, dose-dependent toxicity, and limited clinical efficiency. To make more progress, we integrated the advantages of MDM2 inhibitors and platinum drugs to construct novel Pt-RG7388 (a selective MDM2 inhibitor) complexes. Most complexes, especially and , displayed greatly improved antiproliferative activity against both wild-type and mutated p53 cancer cells.

Discovery of Platinum-Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents.

Recently, artemisinin and derivatives have been revealed to possess encouraging antitumor activity. Herein, we integrated the antitumor advantages of artesunate and platinum drugs to construct novel Pt-artesunate dual-action and triple-action complexes. Most derivatives, especially , displayed broad-spectrum and potent antitumor activities against a number of cancer cell lines.

Inspired by bis-β-carboline alkaloids: Construction and antitumor evaluation of a novel bis-β-carboline scaffold as potent antitumor agents.

Bis-β-carboline alkaloids are widely distributed in natural products and represent a promising drug-like scaffold for discovering drugs and bioactive molecules. In this study, we utilized the structural simplification strategy to construct a novel bis-β-carboline scaffold via "one-pot" condensation-Mannich reaction. The simplified bis-β-carboline derivatives were obtained in good yield.

Discovery of potent tubulin inhibitors targeting the colchicine binding site via structure-based lead optimization and antitumor evaluation.

The colchicine binding site of tubulin is a promising target for discovering novel antitumour agents. Previously, we identified 2-aryl-4-amide-quinoline derivatives displayed moderate tubulin polymerisation inhibitory activity and broad-spectrum antitumour activity. In this study, structure based rational design and systematic structural optimisation were performed to obtain analogues bearing diverse substituents and scaffolds.

Discovery of novel tubulin inhibitors targeting the colchicine binding site via virtual screening, structural optimization and antitumor evaluation.

The colchicine binding site of tubulin is a promising target for discovering novel antitumor agents which exert the antiangiogenic effect and are not susceptible to multidrug resistance. For identifying novel tubulin inhibitors, structure-based virtual screening was applied to identify hit 9 which displayed moderate tubulin polymerization inhibition and broad-spectrum in vitro antitumor activity. Structural optimization was performed, and biological assay revealed analog E27 displayed the best antitumor activity with IC values ranging from 7.