Heronamide C, a polyketide macrolactam antifungal agent synthesized by marine Actinomycetes, exhibits selective toxicity by inhibiting growth and promoting abnormal cell wall material accumulation in wild-type fission yeast cells (MIC = 0.13-0.28 μM), without affecting Gram-positive bacteria or human cancer cell lines, HeLa and MDA-MB-231. At 20 μM, it triggers reversible morphological alterations, notably the development of large intracellular structures, in HeLa cells.
Dynamin-related protein 1 (Drp1) inhibitor, inhibits Drp1 GTPase activity. Displays no effect on dynamin 1 or other mitochondrial dynamics-related proteins. Inhibits mitochondrial fission, dysfunction and reactive oxygen species (ROS) production in vitro.
Ellipticine quinone, also known as NSC-383230, is a Drp1 inhibitor. rpitor1 and Drpitor1a inhibited the GTPase activity of Drp1 without inhibiting the GTPase of dynamin 1. Ellipticine quinone showed greater potency than the current std. Drp1 GTPase inhibitor, mdivi-1, (IC50 for mitochondrial fragmentation are (0.06, and 10 μM, resp.). Ellipticine quinone suppressed lung cancer tumor growth in a mouse xenograft model. Ellipticine quinone also inhibited mitochondrial ROS prodn., prevented mitochondrial fission, and improved right ventricular diastolic dysfunction during IR injury.
Phosphatidic acid is a phospholipid and an intermediate in glycerolipid biosynthesis. It is a transient intermediate in the synthesis of various phospholipid species that is synthesized de novo in cells via multiple routes, including the glycerol-3 phosphate and dihydroxyacetone phosphate pathways, enzymatic conversion of phosphatidylcholine by phospholipase D, and acetylation of lysophosphatidic acid by lysoPA-acyltransferase, among others. It has roles in shaping cellular membranes, cellular signaling, vesicle fission and fusion, as well as mitochondrial division and fusion. It stimulates respiratory burst in neutrophils independent of diacylglycerol and activates monoacylglycerol acyltransferase, phospholipase C (PLC), Ras, and phosphatidylinositol 4-phosphate (PIP4) kinase in several cell lines. Phosphatidic acids (egg) is a mixture of phosphatidic acids isolated from chicken egg with fatty acids of variable chain lengths.