Potent cytotoxic peptides from the Australian marine sponge Pipestela candelabra.

Trong Tran,Ngoc Pham,Ronald Quinn,John Hooper,Gregory Fechner

doi:10.3390/md12063399

Abstract

Two consecutive prefractionated fractions of the Australian marine sponge extract, Pipestela candelabra, were identified to be selectively active on the human prostate cancer cells (PC3) compared to the human neonatal foreskin fibroblast non-cancer cells (NFF). Twelve secondary metabolites were isolated in which four compounds are new small peptides. Their structures were characterized by spectroscopic and chemical analysis. These compounds inhibited selectively the growth of prostate cancer cells with IC50 values in the picomolar to sub-micromolar range. Structure-activity relationship of these compounds is discussed.

Highlights

Pipestela has been characterized as a new sponge genus sharing some shape features and molecularDNA sequences with ten other genera in the family Axinellidae: Auletta, Axinella, Cymbastela, Dragmacidon, Dragmaxia, Pararhaphoxya, Phakellia, Phycopsis, Ptilocaulis, and Reniochalina [1].The genus Pipestela is distributed only across the north-eastern region of Australia, and is very common from the Great Barrier Reef, Coral Sea, Papua New Guinea, Solomon Islands, and Vanuatu [2].Chemical investigation of the sponge P. candelabra was first reported in 2012 with the identificationMar
Hemiasterlins and milnamides are two related small cytotoxic peptide families from marine sponges. Their structural features contain a dipeptide side chain of two unnatural amino acid residues, tert-leucine and N-methylvinylogous valine. This dipeptide fragment is incorporated with another atypical amino acid residue tri- or tetra-methylated tryptophan to produce the hemiasterlins or connected to a tetrahydro-β-carboline residue to form the milnamides
The results indicated that replacing the methylene at carbon at δC 156.8 ppm (C-1) with a carbonyl or an imine led to a decrease in cytotoxicity

Summary

Introduction

Pipestela has been characterized as a new sponge genus sharing some shape features and molecular. A different structure class, hemiasterlin and milnamide analogues, was found in this chemical study on the Australian sponge P. candelabra. Hemiasterlins and milnamides are two related small cytotoxic peptide families from marine sponges Their structural features contain a dipeptide side chain of two unnatural amino acid residues, tert-leucine and N-methylvinylogous valine. Milnamide D [8,9]) have been identified from four sponge genera including Auletta [6,7], Cymbastela [5,9], Hemiasterella [4], and Siphonochalina [6] These related natural products show potent cytotoxicity against many cancer cell lines, such as murine leukemia P388, human breast cancer. P. candelabra (A) and related-hemiasterlin anticancer agents in clinical trial (B)

Results and Discussion

General Experimental Procedures

Animal Material

Extraction and Isolation

Cytotoxicity Assay

Conclusions