Bakteriostatisch wirkende Nitro‐Verbindungen des Thiophens und Furans

Abstract

D a n n , M o l l e r . 23Nr. 1 p 4 7 J ders fur die Thiophenverbindungen IV und VIII, welche sowohl nach Art als auch Starke in ihrem Vermogen ortlich zu hetauben durchaus dem Anctsthesin (I) und Novokain (VI) entsprechen. Auch hemmt keiner der Ester das Wachstum von Streptobacteriuin plantarum in den verwendeten Konzentiationen bis 3 x lo-* g/ccm starker als die analogen Ester der p-Amino-benzoesiiure. Der Grund hierfiir konnte einerseits darin liegen, da13 die Affinitat zii den Haftstellen dieses Wuchsstoffe~~~) sehr viel geringer ware als bei den Sulfonamidenz) ; andererseits konnte an Unterschiede in der Verseifungsgeschwindigkeit der Ester gedacht werden. Daruber hinaus besitzt die Vorstellung groBe Wahrscheinlichkeit, da13 die p-Amino-benzoesaure im Stoffwechsel einer Reaktionsfolge unterliegt, an der die Sulfonaniide his zu einem gewissen Grade teilnehmen konnen, wahrend die empfindliche 4-Amino-naphthoesaure-( 1)20), die wenig hest~ndige5-Amino-thiophen-carh0nsaure-(2)~*) und die unbestandige 5-Amino-furan-~arbons8ure-(2)~~) nebst deren Estern nicht teilnehmen. Die Annahme einer oxydativen Umwandlung erklart am ehesten die Befunde, daB p-Hydroxylamino-henzolsulfonsaureamid in vitro hei Streptokokken viel starker bakteriostatisch wirkt als SulfanilamidZ3), wahrend p-Hydroxylamino-henzoesaure ebenso stark enthemmt wie p-Amino-benzoesaurel). ___ Otto D a n n und E r n s t F r i e d r i c h Moller: Bakteriostatisch wir-kende Nitro-Verbindungen des Thiophens und Furans.

Correlation of Antitumor Activity and Electron Deficiency of Nitrofuranylhydrazone Compounds

“…It has been suggested that nitrofurazone interferes with normal metabolism by virtue of its capacity to be reduced (15). In addition, previous authors have concluded from a study of nitrofurans, nitrothiophenes, nitrobenzenes, and related compounds, that ease of reducibility plays a major role in the antibacterial effectiveness of heterocyclic nitro compounds (16). These authors also proposed a relationship between the redox potential developed by the organism in culture and that required by the inhibitory nitrofuran, implying that interference with microbial reproduction was associated with formation of a reduction product (hydroxylamine) from the nitro compound (17).…”

The Mechanism of Action of Nitro-heterocyclic Antimicrobial Drugs. Metabolic Activation by Micro-organisms

“…This is illustrated in Table 7, in which the activities of four pairs of nitro-and aminoimidazoles are compared. Dann & Moller (1947, 1949 had similarly observed that aminothiophenes and aminofurans were inactive. It is probable that the reactive forms of all of these drugs are partially reduced intermediates which are highly unstable ; likely candidates are the hydroxylamino-or nitroso-derivatives (Dann & Moller, 1949;Paul et al, 1960;McCalla et al, 1970).…”

“…belongs to a class of drugs (including nitrofurans as well as nitroimidazoles) whose antimicrobial activity depends on the presence of the nitro group (Dann & Moller, 1947;Grunberg & Titsworth, 1973). Although members of this class of drugs differ in a number of properties including their spectrum of antimicrobial activity (Grunberg & Titsworth, 1973 ;Edwards, Dye & Carne, 1973)~ studies of the mechanism of action of nitrofurazone (McCalla, Reuvers & Kaiser, I 970), metronidazole (Ings, McFadzean & Ormerod, 1974) and MEV (Goldstein et al, 1977) suggest that the effective target of all of these drugs is DNA.…”

“…It has been known for some time that nitro-organic compounds are reduced by microbial systems (Dann & Moller, 1947) and, recently, reduced derivatives were shown to be reactive and to bind to DNA and to proteins (McCalla et al, 1970;Ings et dl., 1974;Tu & McCalla, 1975). In this paper, we show that metabolic activation (reduction of the nitro group) necessarily accompanies the bactericidal effects of MEV.…”

Mode of Action of Nitrofurazone

“…Incorporation of [3H]nitrofuran into the cold trichloroacetic acid-insoluble fraction of intact cells. Nitrofuran [17 &g(3 ACi)] was used. For other details, see legend ofFig.…”