Compounds, compositions, and methods of agelastatin alkaloids: patent evaluation of WO2015042239 (A1)

ABSTRACT

Agelastatins are a family of tetracyclic alkaloids isolated from marine sponges. The patent examined in this publication covers the chemical synthesis of agelastatins A to F and eight analogues and their therapeutic use against hematologic malignancies. The claim on the chemical synthesis features a novel biomimetic cyclization of a tricyclic precursor, which streamlines scalable access to agelastatins and their analogues. This new synthetic approach can potentially expedite the research on these compounds for therapeutic use against cancers by making them more easily available. The claim on the therapeutic use against hematologic malignancies is based on the in vitro cytotoxicity against a limited number of cell lines and can be further strengthened by in vivo therapeutic evaluations focusing on specific hematologic malignancies. The comparative evaluation of the cytotoxicities of the natural alkaloids described in the application greatly enhances the understanding of their structure-activity relationships (SARs) relevant to the development of novel medicinal leads. Overall, the patent application is strong and has the potential to advance the rapidly expanding agelastatin research.

KEYWORDS:

• Agelastatin alkaloid
• chemical synthesis
• cytotoxicity
• blood cancer
• apoptosis

Article highlights

1. A patent application on the chemical synthesis and anti-cancer activity of agelastatins A to F and eight analogues is examined in this publication. Overall, it is a strong patent application and has the potential to advance the rapidly expanding agelastatin research.

2. The chemical synthesis claim in the application represents a novel scalable synthetic protocol that would streamline the synthesis of various agelastatin analogues and expedite the research of these compounds for therapeutic use against cancers.

3. The biological claims in the application indicate that Agelastatin A and D have significant activity against hematologic cancer cell lines based on in vitro cytotoxicity studies. The claim can be further strengthened by therapeutic evaluation in in vivo models focusing on specific hematologic malignancies.

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Declaration of interest

The authors were recently granted a US patent for their application entitled ‘Treating brain cancer using agelastatin A and analogues thereof’. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

No funding to declare.