The protozoan toxin climacostol and its derivatives: Cytotoxicity studies on 10 species of free-living ciliates

Abstract

Climacostol (5-(Z)-non-2-enyl-benzene-1,3-diol) is a natural toxin isolated from the freshwater ciliated protozoan Climacostomum virens and belongs to resorcinolic lipids, a group of compounds that show antimicrobial, antiparasitic, and anticancer activities. We investigated the cytotoxic activity of the chemically synthesized toxin and its alkyl and alkynyl derivatives on C. virens and nine other common species of free-living freshwater ciliates. Our results show that the cytotoxic potency of climacostol can be modulated by the substitution of the double bond present in the aliphatic chain of the toxin with a single or a triple one that was previously obtained during the synthesis of the unsaturated and saturated derivatives of the parent molecule. We demonstrated that the cytotoxicity level of the molecules considered in this study appears to be inversely correlated to the unsaturation level of their aliphatic chains, and that the potency of their action is also related to the target organism.

Chemical Offense by Means of Toxicysts in the Freshwater Ciliate, Coleps hirtus

“…), Spirostomum ambiguum stock Pol‐5 (Buonanno et al. ), and Spirostomum teres stock Pol‐1 (Buonanno ) were grown in bacterized culture medium as described in Buonanno and Ortenzi (). All ciliates were cultured and handled at room temperature (23 °C ± 1), and used in experiments after 1 d of starvation.…”

The changes in the predatory behavior of the microturbellarian Stenostomum sphagnetorum on two species of toxin-secreting ciliates of the genus Spirostomum

“…Spirostomum ambiguum (approx. 1000 × 60 µm) stock Pol-5 (Buonanno & Ortenzi 2010), Spirostomum teres (approx. 380 × 40 µm) stock Pol-1 (Buonanno 2005) and Blepharisma japonicum (approx.…”

“…Extrusomes are membrane-bound organelles that ciliates evolved in association with their cortex, and have the unique capacity to be discharged in response to a variety of environmental stimuli (Hausmann 1978). Recently, it was shown that S. sphagnetorum is "immune" to several extrusomal toxins such as stentorin from Stentor coeruleus Ehrenberg, 1830 (Buonanno 2005), climacostol from Climacostomum virens Ehrenberg, 1833 (Buonanno 2005;Buonanno et al 2008;Pucciarelli et al 2008;Buonanno & Ortenzi 2010) or blepharismin from Blepharisma japonicum Suzuki, 1954 (unpublished data) and, consequently, the predator is able to capture and ingest these ciliates. On the contrary, S. sphagnetorum is very sensitive to loxodesin(s) from Loxodes striatus Ehrenberg, 1830 (Buonanno 2005; Buonanno et al 2005) or spirostomin from Spirostomum teres Claparède et Lachmann, 1858(Buonanno 2005.…”

DNA binding and oxidative DNA damage induced by climacostol–copper(II) complexes: Implications for anticancer properties

“…Petrelli et al [14] have reported that climacostol can exert a potent antimicrobial activity against a panel of bacterial and fungal pathogens, including Staphylococcus, Streptococcus, Enterococcus, and Candida. Buonanno and Ortenzi [15] demonstrated that the cytotoxic potency of climacostol on free-living freshwater ciliates can be modulated by the substitution of the double bond in the aliphatic chain of the toxin with a single or a triple one. Muto et al [16,17] found that climacostol specifically inhibits respiratory chain complex I in rat liver mitochondria, inducing a consequent generation of reactive oxygen species (ROS).…”