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Recent Patents on Anti-Cancer Drug Discovery

Author(s): Lin Zhang and Lei Zhang*

DOI: 10.2174/1872212115666210615153507

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Santacruzamate A Compositions, Analogs and Methods of Use: A Patent Evaluation of WO 2014/018913 (A2)

Page: [469 - 478] Pages: 10

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Abstract

Background: Santacruzamate A (SCA) is a natural product isolated from a marine cyanobacterium. Activity test results revealed that SCA is a highly potent HDAC2 inhibitor with an IC50 value of 0.112 nM. The IC50 of SCA in inhibiting cancer cell proliferation is 28.3 μM and 1.3μM on HCT116 and HuT-78 cells, respectively.

Objective: To develop HDAC inhibitors with improved activity, SCA analogs were synthesized for the Structure-Activity Relationship (SAR) studies.

Methods: Various substituted groups were introduced into the zinc binging group, linker, and cap regions of SCA by various chemical synthetic methods.

Results: Compared with SCA, the derivatives of SCA did not exhibit improved HDAC2 inhibitory activity. Nevertheless, several molecules such as III-32, III-33, IV-4b, and IV-11 showed improved activity in inhibiting cell proliferation on HCT116 and HuT-78 cells.

Conclusion: Collectively, a potent HDAC2 inhibitor SCA was discovered as a lead compound for further development of selective HDAC inhibitors.

Keywords: Cancer, histone deacetylase 2, inhibitor, santacruzamate A, structure-activity relationship, selectivity.

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