Disease relevance of ISLANDIN

• Chrysophanol and islandicin, two anthraquinones which are structurally related to emodin, were found to be frame-shift mutagens for Salmonella typhimurium strain TA 1537 after metabolic activation [1].
• Toxicity of funiculosin is unique and highly selective for animal species [2].
• New rhodomycin analogs, SS-288A and SS-288B, produced by a Streptomyces violaceus A262 mutant [3].

High impact information on ISLANDIN

• Treatment of tumors in vivo with doxorubicin at doses below the maximally tolerated dose in mice resulted in multiple log cell kill as measured in vitro or in vivo, whereas rhodomycin B was cytotoxic only at dose levels exceeding its maximally tolerated dose [4].
• Funiculosin completely inhibited the reoxidation of cytochrome b whereas the reoxidation of cytochrome c1 exhibited simple first-order kinetics in the presence of this inhibitor, implying that the iron-sulfur cluster is on the direct path of electron transfer from cytochrome b to cytochrome c1 [5].
• Funiculosin is a well-known inhibitor of the mitochondrial respiratory chain, probably acting at the ubiquinone reducing site or center i of QH2-cytochrome c reductase [6].
• Isolation and RNA sequence analysis of cytochrome b mutants resistant to funiculosin, a center i inhibitor of the mitochondrial ubiquinol-cytochrome c reductase in Saccharomyces cerevisiae [6].
• Changes are described that are brought about by antimycin, NoHOQnO, funiculosin, myxothiazol and mucidin in the alpha-, beta- and gamma-absorption bands of reduced and oxidized cytochromes b in the isolated complex bc1 form beef heart mitochondria [7].

Biological context of ISLANDIN

• Funiculosin; a new specific inhibitor of the respiratory chain in rat liver mitochondria [8].
• After sequencing most of the gene of eel cytochrome b and comparing the deduced amino acid sequence with that of other fish and animals, we hypothesize that the decreased binding of funiculosin could be due to a few amino acid replacements in the third and fourth transmembrane helix of the protein [9].

Anatomical context of ISLANDIN

• The effect of antimycin A and funiculosin, two inhibitors which block electron transfer in the b-c1 complex, on electron flow and electrochemical potential difference of H+ ions in mitochondria at static head (state 4) is investigated [10].

Associations of ISLANDIN with other chemical compounds

• Allelism relationships between diuron-resistant, antimycin-resistant and funiculosin-resistant loci of the mitochondrial map in Saccharomyces cerevisiae [11].
• Modification of aklavinone and aclacinomycins in vitro and in vivo by rhodomycin biosynthesis gene products [12].
• This heterogeneity is removed by the Qi site inhibitors antimycin A, funiculosin and HQNO, but not by the Qo site inhibitors myxothiazol or stigmatellin; (3) of all inhibitors tested only funiculosin had a large effect on the Em/pH profile of either haem b [13].

Gene context of ISLANDIN

• Additionally, the reductase activity of fish mitochondria is resistant to some powerful inhibitors that bind to cytochrome b, in particular to funiculosin [9].
• Funiculosin also induces the oxidation of cytochromes cc1 and an extra reduction of cytochrome b in the aerobic steady state, and it inhibits duroquinol-cytochrome c reductase activity in isolated Complex III [14].

Analytical, diagnostic and therapeutic context of ISLANDIN

• These three inhibitors, and also funiculosin, have been further studied by characterizing their effects on the visible absorbance, magnetic circular dichroism and EPR spectra of the complex and also on the potentiometric properties of the individual metal centers present in the complex [15].

References