Chloroquine-containing compounds: a patent review (2010 – 2014)

Abstract

Repurposing efforts have dominantly focused on racemic CQ with no studies exploring the effect of the (R) and (S) enantiomers, which might potentially have additional benefits in other diseases. Additionally, evaluating other similarly acting antimalarials in clinical use and structural analogs could help maximize the intrinsic value of the 4-aminoquinolines. With regard to cancer therapy, successful repurposing of CQ-containing compounds will require linking the mode of action of these antimalarials with the signaling pathways that drive cancer cell proliferation to facilitate the development of a 4-amino-7-chloroquinoline that can be used as a synergistic partner in anticancer combination chemotherapy.

Autophagy Modulation in Cancer: Current Knowledge on Action and Therapy

“…Autophagy inhibitors include PI3K inhibitors, cycloheximide, vacuolar-type H(+)-ATPase inhibitors, lysosomal lumen alkalizers, and acid protease inhibitors [ 42 ]. Chloroquine (CQ) and hydroxychloroquine (HCQ) are both lysosomal inhibitors previously used for the prevention and treatment of some types of malaria [ 46 ]. Another unconventional drug, azithromycin, a macrolide antibiotic often used for treatment of multiple bacterial infections, was discovered as an autophagy inhibitor after usage in cystic fibrosis patients as an anti-inflammatory drug.…”

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

“…147,287,288 Therefore, the activation of STAT3 by constitutive DNA damage in cancer cells could facilitate selective drug effects on the tumor nest through the circulation, while having discrete indirect effects on the local tissue microenvironment owing to the secretome of the tumor. 292,293 In contrast to genomics, there does not seem to be a major change of research support in sight for high-capacity molecular innovation. To some extent, cellular targeting by CQs can be achieved by conjugation with specific moieties, including sugar groups, and by the generation of hybrid molecules, such as CQ-artemisinin.…”

“…On the other hand, in spite of the widely recognized dose-limiting toxicity of CQs, the technology of molecular carriers for CQs or similar agents to reprogram immune responses, with cellselectivity and retaining direct antineoplastic activity at a low dose, is not yet close to clinical use. 292,293 In contrast to genomics, there does not seem to be a major change of research support in sight for high-capacity molecular innovation. [294][295][296] Furthermore, exploration of molecular concepts cannot be covered by biopharmaceutical industries, due to the fact that the concepts address essentially basic research.…”

Development and Validation of an Hilic–MS/MS Method by One-Step Precipitation for Chloroquine in Miniature Pig Plasma

“…Although it has lost its preeminent position in malaria therapy, there is ample clinical evidence that chloroquine, and its derivative hydroxychloroquine, are effective for the treatment of lupus erythematosus, even during pregnancy. Chloroquine and its analogs have also been shown to modify cell differentiation and induce apoptosis in different cancer cell lines, giving hope that they will prove useful adjuncts to cancer chemotherapy [2]. As an autophagy inhibitor, chloroquine co-medication strongly enhanced in vitro tumor proliferation rate of docetaxel-loaded PEG-b-PLGA micelles [3], and it also played as a chemical sensitizer in doxorubicin and chloroquine coencapsulated liposomes [4].…”