Bacillamide F, Extracted from Marine Bacillus atrophaeus C89, Preliminary Effects on Leukemia Cell Lines

Abstract

Developing new treatments for leukemia is essential since current therapies often suffer from drug resistance and toxicity. Bacillamides are very promising, naturally occurring compounds with various bioactivities. In the present study, we investigated the use of bacillamide analogues, a new thiazole alkaloid bacillamide F that was isolated from marine Bacillus atrophaeus C89 associated with sponge Dysidea avara. The structure of the new compound bacillamide F with indolyl−thiazolyl−pyrrolidine ring was determined by high resolution mass spectrometry, secondary mass spectrometry, and nuclear magnetic resonance analyses. Intriguingly, bacillamide F is able to inhibit the proliferation of an acute myeloid leukemia cell line HL60 (IC50 (24 h) 21.82 µM), and an acute T-cell leukemia Jurkat (IC50 (24 h) 46.90 µM), rather than inhibit the proliferation of the acute histiocytic lymphoma U-937 cell line, human fetal lung fibroblast MRC-5 cell line, and some solid tumor cell lines (IC50 (24 h) > 100 µM). The study provides a new indication of the pharmacological activity of natural product bacillamides.

Keywords: Bacillus atrophaeus; antiproliferation effect; bacillamide; leukemia.

Figure 1

The bacillamide family structures of compounds: (a) This represents the known bacillamide compounds (bacillamide A–E); (b) This represents the new compound, bacillamide F.

Figure 2

The key 2D NMR correlations of bacillamide F.

Figure 3

The plausible biosynthesis pathway of bacillamide F. The biosynthetic process of NRPS (EIM09914.1, bacitracin synthetase) domains, Ox (oxidase domain, EIM09913.1), and AADC (aromatic L-amino acid decarboxylase) domain were involved in the synthesis of bacillamide F. Each circle represents an NRPS enzymatic domain, from left to right: A, adenylation domain, Cy, cyclization domain. C, condensation domain, and PCP, peptidyl carrier protein domain.

Figure 4

MTS assay on three different leukemia cell lines: Jurkat (A–C), HL60 (D–F), and U937 (G–I). Cell availability has been tested for 24, 48 and 72 h by incubating the cells in a 96-well plate with different concentrations of BF (Bacillamide F) (6.25–100 µM). The percentage of control samples (DMSO, 100%) is shown as means ± SDs (n = 3, biological replicates). The experiments were repeated at least twice independently with similar results, and the representative data from one experiment are shown (n = 3, biological replicates).