NONACTIN

Nonactin (6833-84-7) is a monovalent cation ionophore with high selectivity for NH4+ and K+ .1 Upregulates levels of mitochondrial stress proteins HSP58 and GRP75.2 Nonactin abolishes mitochondrial membrane potential.3

Light yellow powder

Nonactin is an ionophore antiobiotic that selectively binds K+and NH4+.

Nonactin is the smallest member of the macrotetrolide complex produced by a range of Streptomyces species. Originally the name, nonactin, reflected the lack of biological activity. The literature is confusing in this respect, as virtually all sources of nonactin are contaminated with small amounts of the much more active monactin. The BioAustralis nonactin has been purified to remove traces of other biologically-active macrotetrolides. Like the other macrotetrolides, nonactin is a monovalent cation ionophore with high selectivity for ammonium and potassium.

ChEBI: Nonactin is a macrotetrolide.

Monovalent cation ionophore that displays selectivity for K + and NH 4 + (K + = NH 4 + > Na + > Mg 2+ > Li + >> Ca 2+ for nonactin-EVA sensor). Induces cation transport across artificial membranes. Also inhibits P-glycoprotein-mediated efflux of chemotherapeutic agents in multiple-drug resistant cancer cells. Antibiotic.

This macrotetrolide antibiotic crystallises from MeOH as colourless needles and is dried at 90o/20hours/high vacuum. [Cordaz et al. Helv Chim Acta 38 1445 1955, crystal structure: Dobler Helv Chim Acta 55 1371 1972, Gambos et al. Tetrahedron Lett 3391 1975, Beilstein 19/12 V 751.]

The antibiotic Nonactin is an ionophore that binds and transports monovalent cations across membranes through passive diffusion. Nonactin displays both antibacterial and anti-tumor activities, and inhibits drug efflux in multiple drug resistant cancers. Naturally occurring Nonactin is composed of four monomers of Nonactic acid, comprised of an equal number of and monomers. The antibiotic properties of Nonactin result from its ability to form stable complexes with monovalent cations; artificial Nonactin tetramers, comprised of either all or all Nonactic acid monomers, lack ion binding ability and are less potent antibiotics. Treatment of erythrocytes with Nonactin leads to suicidal erythrocyte death as evidenced by the shrinking of erythrocytes and translocation of phosphatidylserine from the erythrocyte interior to the cell surface. Nonactin selectively induces apoptosis and results in tumor regression in a β-catenin mutant HCT 116 xenograft model, and can inhibit the surface expression of endogenous HSP60.

[1] CARLOS ALEXANDRE BORGES GARCIA  Graciliano de O N  Laércio Rover Júnior. Determination of potassium ions in pharmaceutical samples by FIA using a potentiometric electrode based on ionophore nonactin occluded in EVA membrane[J]. Journal of pharmaceutical and biomedical analysis, 2003, 31 1: Pages 11-18. DOI:10.1016/s0731-7085(02)00598-8
[2] L. MIZZEN. Identification, characterization, and purification of two mammalian stress proteins present in mitochondria, grp 75, a member of the hsp 70 family and hsp 58, a homolog of the bacterial groEL protein.[J]. The Journal of Biological Chemistry, 1989, 8 1: 20664-20675. DOI:10.1016/s0021-9258(19)47115-9
[3] A K DUDANI. Effects of antimitotic and antimitochondrial agents on the cellular distribution of microtubules and mitochondria.[J]. Cytobios, 1990, 63 253: 95-108.