Serpulanines A to C, N-Oxidized Tyrosine Derivatives Isolated from the Sri Lankan Fungus Serpula sp.: Structure Elucidation, Synthesis, and Histone Deacetylase Inhibition

David E Williams; Niranjan W Gunasekara; Pamoda B Ratnaweera; Zehua Zheng; Samantha Ellis; Sarah Dada; Brian O Patrick; Ravi L C Wijesundera; Chandrika M Nanayakkara; Wilfred A Jefferies; E Dilip de Silva; Raymond J Andersen

doi:10.1021/acs.jnatprod.7b00680

Serpulanines A to C, N-Oxidized Tyrosine Derivatives Isolated from the Sri Lankan Fungus Serpula sp.: Structure Elucidation, Synthesis, and Histone Deacetylase Inhibition

J Nat Prod. 2018 Jan 26;81(1):78-84. doi: 10.1021/acs.jnatprod.7b00680. Epub 2018 Jan 5.

Affiliations

¹ Departments of Chemistry and Earth, Ocean & Atmospheric Sciences, University of British Columbia , 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
² Departments of Chemistry and Plant Science, University of Colombo , Colombo 03, Sri Lanka.
³ Department of Science and Technology, Uva Wellassa University , Badulla, Sri Lanka.
⁴ The Michael Smith Laboratories; Vancouver Prostate Centre; Departments of Medical Genetics, Microbiology & Immunology, and Zoology; and The Centre for Blood Research and Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, BC, Canada.
⁵ Department of Chemistry, University of British Columbia , 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.

PMID: 29303267
DOI: 10.1021/acs.jnatprod.7b00680

Abstract

Serpulanines A (1), B (2), and C (3) have been isolated from extracts of the rare Sri Lankan macrofungus Serpula sp. The structures of 1, 2, and 3 were elucidated by a combination of spectroscopic and single-crystal X-ray diffraction analyses. Serpulanines A (1) and B (2) both contain the rare (E)-2-hydroxyimino hydroxamic acid functional group array. A proposed biogenesis for serpulanine B (2) suggests that its (E)-2-hydroxyimino hydroxamic acid moiety arises from a diketopiperazine precursor. Synthetic serpulanine A (1) inhibited class I/II histone deacetylases in murine metastatic lung carcinoma cells with an IC₅₀ of 7 μM.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Basidiomycota / chemistry*
Cell Line, Tumor
Crystallography, X-Ray / methods
HeLa Cells
Histone Deacetylase Inhibitors / chemistry*
Histone Deacetylase Inhibitors / isolation & purification
Histone Deacetylase Inhibitors / pharmacology*
Humans
Hydroxamic Acids / chemistry
Hydroxamic Acids / pharmacology
Lung Neoplasms / drug therapy
Mice
Oxidation-Reduction
Tyrosine / analogs & derivatives*
Tyrosine / chemistry
Tyrosine / isolation & purification
Tyrosine / pharmacology*

Substances

Histone Deacetylase Inhibitors
Hydroxamic Acids
Tyrosine