Crambescidin-816 Acts as a Fungicidal with More Potency than Crambescidin-800 and -830, Inducing Cell Cycle Arrest, Increased Cell Size and Apoptosis in Saccharomyces cerevisiae

Abstract

In this paper, we show the effect of crambescidin-816, -800, and -830 on Saccharomyces cerevisiae viability. We determined that, of the three molecules tested, crambescidin-816 was the most potent. Based on this result, we continued by determining the effect of crambescidin-816 on the cell cycle of this yeast. The compound induced cell cycle arrest in G2/M followed by an increase in cell DNA content and size. When the type of cell death was analyzed, we observed that crambescidin-816 induced apoptosis. The antifungal effect indicates that crambescidins, and mostly crambescidin-816, could serve as a lead compound to fight fungal infections.

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…Rubiolo and colleagues investigated the guanidine antifungal alkaloid crambescidin-816 ( 51 ), previously isolated from the Mediterranean sponge Crambe crambe [62]. Detailed cell cycle studies in the yeast Saccharomyces cerevisiae demonstrated that this compound induced G2/M cell cycle arrest followed by apoptosis and mitochondrial disfunction, suggesting that although cytotoxic crambescidin-816 “….could serve as a lead compound to fight fungal infections”.…”

Marine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model

“…Several of these molecules have been patented due to their cytotoxic, antifungal and antiviral activities and some of them, as for example crambescidin 816 (C816), also have recognized effects over calcium ion channels [3, 5, 6]. Furthermore, in 2007 crambescidin 800 (C800) was also proposed as an antioxidant agent against hypoxia, nitric oxide and glutamate-induced oxidative stress [7].…”

Polycyclic Guanidine Alkaloids from Poecilosclerida Marine Sponges

“…Compared to TGA class 3, TGA class 2 is less active, although batzelladine C ( 28 ) and L ( 38 ) and dehydrobatzelladine C ( 35 ), in general, exhibited a GI 50 below 1 µg/mL [ 73 ]. Finally, crambescidin 816 ( 3 ) was shown to inhibit cell migration by altering the cytoskeleton dynamics and induced cell death by apoptosis [ 75 , 78 ].…”