08 January 2020
Protein kinases are drug targets for several therapeutic areas. Many investigated protein kinase inhibitors are natural product small molecules or their derivatives. Marine-derived products from sources such as bacteria and cyanobacteria, fungi, animals, algae, soft corals, sponges etc, have been found to have potent kinase inhibitory activity, or desirable pharmacophores which merit further development.
A review of marine derived natural product kinase inhibitors, reported between 2014-2019, indicated that there is vast opportunity for kinase inhibitor research on the natural product chemistry from marine sources, with soft coral of particular interest.
It was noted that of the 58 kinase inhibitors that had been reported from marine animals, marine soft corals and marine sponges, many are likely to be produced by symbiotic microorganisms. It is therefore necessary to consider that these conditions may be difficult or indeed impossible to cultivate in laboratory conditions. Considering this, it is deemed important that the development of selective kinase inhibitors from marine natural drug discovery leads utilise fragment (pharmacophore) based medicinal chemistry to overcome the supply limitations of natural product drug leads.
The review revealed that during the period under review 22 natural product kinase inhibitors were isolated from marine bacteria. Marine fungi gave rise to 16 new kinase inhibitors, while marine animals were the source of 14 new kinase inhibitors and 10 kinase inhibitors were derived from marine algae. In addition, 42 new natural product kinase inhibitors were reported after being isolated from marine sponges and two were derived from marine soft coral.
The study noted that in recent years new techniques, including deep-sea sampling, advanced methods in chemical synthesis, more efficient target-based isolation, along with computational database mining strategies and high-throughput screenings, have been helpful for drug candidate discovery and design.
The study also highlighted that while most of the approved kinase inhibitors are ATP binding site competitors, it is critical to overcome the toxicity associated with this liability. Hence marine-derived natural product kinase inhibitors could serve as lead compounds for development by medicinal chemistry.
Marine Drugs: DOI.org/10.3390/md17090493
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