Antiproliferative Activity of Mycalin A and Its Analogues on Human Skin Melanoma and Human Cervical Cancer Cells.

Domenica Capasso,Nicola Borbone,Vincenzo Piccialli,Monica Terracciano,Sonia Di Gaetano

doi:10.3390/md18080402

Domenica Capasso, Nicola Borbone + Show 3 more

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https://doi.org/10.3390/md18080402

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Abstract

Mycalin A, a polybrominated C15 acetogenin isolated from the encrusting sponge Mycale rotalis, displays an antiproliferative activity on human melanoma (A375) and cervical adenocarcinoma (HeLa) cells and induces cell death by an apoptotic mechanism. Various analogues and degraded derivatives of the natural substance have been prepared. A modification of the left-hand part of the molecule generates the most active substances. A structurally simplified lactone derivative of mycalin A, lacking the C1–C3 side chain, is the most active among the synthesized compounds exhibiting a strong cytotoxicity on both A375 and HeLa cells but not but not on human dermal fibroblast (HDF) used as healthy cells. Further evidence on a recently discovered chlorochromateperiodate-catalyzed process, used to oxidise mycalin A, have been collected.

Highlights

C15 acetogenins are typical metabolites from red algae belonging to the genus Laurencia
In this paper we report that mycalin A (1) and some of its synthetic analogues (4–11) possess a strong antiproliferative activity on human melanoma (A375) and human cervical adenocarcinoma (HeLa) cells
All the cells were incubated with mycalin A at a 10 μM concentration for 48 h

Summary

Introduction

C15 acetogenins are typical metabolites from red algae belonging to the genus Laurencia They are usually halogenated substances including one or more cyclic ethers with different ring sizes and an enyne or a bromoallene terminal unit [1]. In 1990 three new members of this class of substance (mycalin A–C, 1–3, Figure 1) (†) were isolated by our group from the encrusting sponge Mycale rotalis [5,6] collected in Italy along the Sicily coast. This finding was rather unusual and was explained by hypothesizing that the sponge could preferentially grow on an alga of the Laurencia species engulfing it entirely. This agrees well with the findings by Rinehart et al [7] who had previously shown that metabolites peculiar to Laurencia species could be detected from other marine organisms

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