Microtubule-stabilizing drugs from marine sponges: focus on peloruside A and zampanolide

Abstract

Marine sponges are an excellent source of bioactive secondary metabolites with potential therapeutic value in the treatment of diseases. One group of compounds of particular interest is the microtubule-stabilizing agents, the most well-known compound of this group being paclitaxel (Taxol), an anti-cancer compound isolated from the bark and leaves of the Pacific yew tree. This review focuses on two of the more recent additions to this important class of drugs, peloruside A and zampanolide, both isolated from marine sponges. Peloruside A was isolated from Mycale hentscheli collected in New Zealand coastal waters, and it already shows promising anti-cancer activity. Two other potent bioactive compounds with different modes of action but isolated from the same sponge, mycalamide A and pateamine, will also be discussed. The fourth compound, zampanolide, most recently isolated from the Tongan sponge Cacospongia mycofijiensis, has only recently been added to the microtubule-stabilizing group of compounds, and further work is in progress to determine its activity profile relative to peloruside A and other drugs of this class.

Keywords: microtubule stabilization; mycalamide; pateamine; peloruside; zampanolide.

Figure 1

Structures of the compounds.

Figure 2

The marine sponge Mycale hentscheli collected from Pelorus Sound, New Zealand.

Figure 3

Peloruside A-induced tubulin polymerization in 1A9 ovarian carcinoma cells. Cells were treated with peloruside A and a supernatant and pellet fraction electrophoresed. The gel was immunoblotted for α-tubulin. Image supplied by Arun Kanakkanthara.

Figure 4

Cacospongia mycofijiensis, collected from Vava’u, Tonga. Photograph courtesy of Karen Stone, Dive Vava’u.

Figure 5

Effect of zampanolide on cell cycle progression using flow cytometry. HL-60 promyelocytic leukemic cells were treated with 4 nM zampanolide for 16 hr, stained with propidium iodide, and analyzed by flow cytometry. Graphs courtesy of Jessica Field.