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In a search of small molecules active against apoptosis-resistant cancer cells, a skeletal rearrangement of alkaloid haemanthamine was utilized to generate a series of compounds possessing the alkaloid montanine ring system. The synthesized compounds were found to inhibit proliferation of cancer cells resistant to apoptosis at micromolar concentrations. Selected compounds were also active against patient-derived glioblastoma cells expressing stem-cell markers. This is the first report describing the preparation of synthetic analogues of the montanine-type alkaloids with antiproliferative activity. The compounds prepared in the current investigation appear to be a useful starting point for the development of agents to fight cancers with apoptosis resistance, and thus, associated with poor prognoses.

A new diacylguanidine, actinofide (1), has been isolated from the marine mollusk Actinocyclus papillatus. The structure, exhibiting a guanidine moiety acylated by two terpenoid acid units, has been established by spectroscopic methods and secured by synthesis. Following this, a series of structural analogues have been synthesized using the same procedure. All of the compounds have been evaluated in vitro for the growth inhibitory activity against a variety of cancer cell lines.

The use of a response surface model offers the possibility of reducing the experiments while determining accurately the optimal combinations. We herein highlighted that combining the Na/K/2Cl cotransporter and/or anion exchanger inhibitor Sph A with chemotherapeutic agents could improve the therapeutic benefits of conventional chemotherapies against advanced melanomas, particularly because Sph A exerts cytotoxic effects regardless of the genetic BRAF and NRAS status.

We disclose novel amphiphilic ruthenium and osmium complexes that auto-assemble into nanomedicines with potent antiproliferative activity by inhibition of mitochondrial respiration. The self-assembling units were rationally designed from the [M(p-cymene)(1,10-phenanthroline)Cl]PF6...