Actinomycin. Chemistry and mechanism of action

Phenoxazine Compounds Produced by the Reactions with Bovine Hemoglobin Show Antimicrobial Activity Against Non-tuberculosis Mycobacteria

“…Though phenoxazines are found in the actinomycins (Brockmann and Muxfeldt 1956;Hollstein 1974), in various insect pigments called ommochromes (Butenandt et al 1960), and in some microorganism metabolites (Anzai et al 1960), and chemically synthesized by oxidative condensation of o-aminophenol and its derivatives (Gerber and Lechvalier 1964;Hishida et al 1974), the biological effects of the phenoxazines remained obscure, except for actinomycin D, which shows strong anti-cancer effects by inhibiting DNA dependent RNA polymerase (Hollstein 1974). Chemically synthesized phenoxazines seemed to have little anti-microbial effects (Gerber and Lechevalier 1964) and anti-cancer effects (Motohashi et al 1991), probably because of poor solubility in water.…”

Interaction of actinomycin D with yeast ribosomal RNA

“…However, this binding is much weaker than the binding of AM to DNA and could be detected only with highly sensitive methods. Since RNA in solution has an A-conformation, the interaction of AM with rRNA should have a molecular basis different from that suggested for the intercalation complex of AM with DNA for which a B-conformation of the helix is a prerequisite [5]. Further experiments are necessary to clarify the nature of binding between AM and RNA.…”

“…The binding of AM to RNA has not been reported, probably because of the low binding affinity and the lack of sensitivity in the methods used [5]. In an extensive study of 5 different techniques, equilibrium dialysis was considered to be most reliable assay for studying the binding of AM [6].…”

2-Aminophenoxazine-3-one induces cellular apoptosis by causing rapid intracellular acidification and generating reactive oxygen species in human lung adenocarcinoma cells

“…Phx-3 did not seem to permeate to the nucleus in our study; however, the possibility that a small amount of Phx-3 permeated to the nucleus could not be ruled out. Phx-3 intercalates to DNA in a cell-free system (36) as actinomycin D does (20), but whether the function of the genomic DNA was affected by the intercalation of Phx-3 in A549 cells is unclear.…”

“…Phenoxazine compounds including 2-amino-4, 4·-dihydro-·, 7-dimethyl-3H-phenoxazine-3-one (Phx-1), and 2-aminophenoxazine-3-one (Phx-3), which are synthesized by the reactions of o-aminophenols with bovine hemoglobin (18,19), are oxidative phenoxazines like actinomycin D (20) and exert anticancer activity against various cancer cells in vitro and in vivo, promoting cellular apoptosis (21)(22)(23) 2-Aminophenoxazine-3-one induces cellular apoptosis by causing rapid intracellular acidification and generating reactive oxygen species in human lung adenocarcinoma cells caspase-dependent apoptosis in multiple myeloma cells (24), and caspase-independent apoptosis in neuroblastoma cells, glioma cells and gastric cancer cells (25)(26)(27). However, it remains unclear how pHi is affected, and how ROS and NF-κB are implicated in the apoptosis of cancer cells in the presence of Phx-3.…”