Antitumor Effects of Two Novel Naturally Occurring Terpene Quinones Isolated from the Mediterranean Ascidian Aplidium conicum

Abstract

The ascidian Aplidium conicum collected along Sardinia coasts (Italy) contained two novel prenylated benzoquinones, designated thiaplidiaquinone A (1) and thiaplidiaquinone B (2). These compounds showed an unprecedented tetracyclic structure. We have studied the pro-apototic mechanisms of both prenylated benzoquinones in the Jurkat cell line that is derived from a human T lymphoma, and we show that both compounds induce a strong production of intracellular reactive oxygen species (ROS) in this cell line. Moreover, kinetic experiments, comparing the timing of ROS induction with the collapse of the mitochondria potential (DeltaPsi(m)), clearly showed that ROS preceded the disruption of the mitochondrial potential, and the later one paralleled the appearance of apoptotic cells. Thus, thiaplidiaquinones A and B can enter into the cells and induce cell death by apoptosis.

Quinone and Hydroquinone Metabolites from the Ascidians of the Genus Aplidium

“…Both compounds were able to induce apoptosis in Jurkat cell lines that were derived from a human T lymphoma through the overproduction of reactive oxygen species (ROS), which mediated the collapse of the mitochondrial potential (ΔΨ m ). The thiaplidiaquinones 50 and 51 exhibited cytotoxic activity against the human leukemia T cell line Jurkat cells, with an IC 50 of approximately 3 μM [55]. The total synthesis of thiaplidiaquinone A ( 50 ) was described by Carbone [56], while the biomimetic synthesis of thiaplidiaquinone A and B was developed by Copp around the same time [57].…”

Recent advances in 1,4-benzoquinone chemistry

“…[39][40][41][42] Vast amount of research has been carried out to establish the antitumor activity of quinones. [43][44][45][46][47] Aiello et al 48 isolated two novel prenylated benzoquinones thiaplidiaquinone A (11) and thiaplidiaquinone B (12) from the Mediterranean ascidian Aplidium conicum. Both thiaplidiaquinones can enter into the cell and induce cell death by apoptosis.…”

“…64 They are characterized by pronounced and manifold biological properties. 65 For instance, Kobayashi and co-workers [66][67][68][69] have done a pioneering work in isolating a series of nakijiquinones A-I which are of particular relevance among sesquiterpenoid quinones (45)(46)(47)(48)(49)(50)(51)(52)(53). Stahl et al 70 described the first enantioselective total synthesis of the nakijiquinones and their biological evaluation.…”

Aplicyanins – brominated natural marine products with superbasic character

“…In particular, natural products from the sea attract particular attention. Numerous nitrogen-containing metabolites belonging to unprecedented structural families and possessing interesting biological properties such as antitumor activity or cytotoxicity have been obtained from marine tunicates of the genus aplidium [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. In their search for new antitumor agents from marine organisms, Reyes et al [16] isolated from Aplidium cyaneum the cytotoxic and antimicotic alkaloids aplicyanins A-F (see Fig.…”