ferroquine and Neoplasms

Malaria and cancer are chronic diseases. The challenge with drugs available for the treatment of these diseases is drug toxicity and resistance. Ferrocene is a potent organometallic which have been hybridized with other compounds resulting in compounds with enhanced biological activity such as antimalarial and anticancer. Drugs such as ferroquine were developed from ferrocene and chloroquine. It was tested in the 1990s as an antimalarial and is still an effective antimalarial. Many researchers have reported ferrocene compounds as potent compounds useful as anticancer and antimalarial agents when hybridized with other pharmaceutical scaffolds. This review will be focused on compounds with ferrocene moieties that exhibit either an anticancer or antimalarial activity.

Topics: Aminoquinolines; Antimalarials; Antineoplastic Agents; Chloroquine; Drug Resistance, Neoplasm; Drug Therapy, Combination; Ferrous Compounds; Humans; Malaria; Metallocenes; Neoplasms; Plasmodium falciparum

Despite the tremendous progress in medicine, cancer remains one of the most serious global health problems awaiting new effective therapies. Here we present ferroquine (FQ), the next generation antimalarial drug, as a promising candidate for repositioning as cancer therapeutics. We report that FQ potently inhibits autophagy, perturbs lysosomal function and impairs prostate tumor growth in vivo. We demonstrate that FQ negatively regulates Akt kinase and hypoxia-inducible factor-1α (HIF-1α) and is particularly effective in starved and hypoxic conditions frequently observed in advanced solid cancers. FQ enhances the anticancer activity of several chemotherapeutics suggesting its potential application as an adjuvant to existing anticancer therapy. Alike its parent compound chloroquine (CQ), FQ accumulates within and deacidifies lysosomes. Further, FQ induces lysosomal membrane permeabilization, mitochondrial depolarization and caspase-independent cancer cell death. Overall, our work identifies ferroquine as a promising new drug with a potent anticancer activity.

Topics: Aminoquinolines; Animals; Antimalarials; Antineoplastic Agents; Autophagy; Caspases; Cell Cycle Checkpoints; Cell Death; Cell Line, Tumor; Cell Proliferation; Chloroquine; Female; Ferrous Compounds; Hydrogen-Ion Concentration; Intracellular Membranes; Lysosomes; Metallocenes; Mice, Nude; Neoplasms; Permeability; Stress, Physiological; Xenograft Model Antitumor Assays