Antibiotic YC 73 of Pseudomonas origin. 3. Synthesis of thioformin analogues.
In the earlier paper of this series1}, it was reported that YG 73 (I) of a Pseudomonas origin was a cupric complex of an acidic substance named thioformin (II), which could be synthesized by treating N-methylhydroxylamine with potassium dithioformate. Soon after the structure determination of II, the fact that such a simple thiohydroxamic acid derivative as II possesses significant antimicrobial activity prompted us to synthesize structural analogues of II. The analogues represented in the general formula III were readily prepared by the following methods. R\ yS )N-Cf (III) ho/ \h Method A : Direct thioformylation of N-substituted hydroxylamines with potassium dithioformate.
DNA damage and reticular stress in cytotoxicity and oncotic cell death of MCF-7 cells treated with fluopsin C
ABSTRACT Fluopsin C is an antibiotic compound derived from secondary metabolism of different microorganisms, which possesses antitumor, antibacterial, and antifungal activity. Related to fluopsin C antiproliferative activity, the aim of this study was to examine the following parameters: cytotoxicity, genotoxicity, cell cycle arrest, cell death induction (apoptosis), mitochondrial membrane potential (MMP), colony formation, and mRNA expression of genes involved in adaptive stress responses and cellular death utilizing a monolayer. In addition, a three-dimensional cell culture was used to evaluate the effects on growth of tumor spheroids. Fluopsin C was cytotoxic (1) producing cell division arrest in the G1 phase, (2) elevating expression of mRNA of the CDKN1A gene and (3) decrease in expression of mRNA H2AFX gene. Further, fluopsin C enhanced DNA damage as evidenced by increased expression of mRNA of GADD45A and GPX1 genes, indicating that reactive oxygen species (ROS) may be involved in the observed genotoxic response. Reticulum stress was also detected as noted from activation of the ribonuclease inositol-requiring protein 1 (IRE1) pathway, since a rise in mRNA expression of the ERN1 and TRAF2 genes was observed. During the cell death process, an increase in mRNA expression of the BBC3 gene was noted, indicating participation of this antibiotic in oncotic (ischemic) cell death. Data thus demonstrated for the first time that fluopsin C interferes with the volume of tumor spheroids, in order to attenuate their growth. Our findings show that fluopsin C modulates essential molecular processes in response to stress and cell death.
Mangone's concise marine almanac
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