Scalable Total Synthesis, IP3R Inhibitory Activity of Desmethylxestospongin B, and Effect on Mitochondrial Function and Cancer Cell Survival

Abstract

The scalable synthesis of the oxaquinolizidine marine natural product desmethylxestospongin B is based on the early application of Ireland-Claisen rearrangement, macrolactamization, and a late-stage installation of the oxaquinolizidine units by lactam reduction. The synthesis serves as the source of material to investigate calcium signaling and its effect on mitochondrial metabolism in various cell types, including cancer cells.

Marine Compounds, Mitochondria, and Malignancy: A Therapeutic Nexus

“…c, caspase-3, and Bax concentration, and decreased the MMP in LOVO cells [ 96 ]. Desmethylxestospongin B, also known as dmXe B, is a complex marine natural compound that displays unique capabilities as a calcium pathway modulator and has downstream impacts in the mitochondrial metabolism of cancer cells [ 97 ]. Through the suppression of inositol-1,4,5-triphosphate receptors, xestospongin B was able to exert an effect on mitochondrial metabolism.…”

“…Through the suppression of inositol-1,4,5-triphosphate receptors, xestospongin B was able to exert an effect on mitochondrial metabolism. This was accomplished via regulating calcium communication between the endoplasmic reticulum (ER) and mitochondria that resulted in a decrease in mitochondrial respiration, which in turn caused the stimulation of AMPK and autophagy [ 97 ]. The sulfated polysaccharide (EI-SP), a compound that is present in marine algae and isolated from Enteromorpha intestinalis, has been demonstrated to have antioxidant, antineoplastic, and anti-inflammatory properties [ 98 ].…”