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Journal ArticleDOI

Effect of some arylguanidino- and arylaminopyrimidines on the growth of certain microorganisms

01 Feb 1961-Archives of Biochemistry and Biophysics (Academic Press)-Vol. 92, Iss: 2, pp 366-372

TL;DR: 2,4-Bis(arylamino)-6-hydroxypyrimidines have been found to be the most active of the series and their inhibitory activity seems to be partially due to their interference with the pyrimidine metabolism of the microorganisms.

Abstract2,4-Diamino-6-hydroxypyrimidine and its derivatives obtained by the replacement of C-2 and/or C-4 amino group by various para -substituted arylamino or arylguanidino groups have been investigated for their inhibitory action on the growth of Streptococcus faecalis, Lactobacillus arabinosus , and Escherichia coli . 2,4-Bis(arylamino)-6-hydroxypyrimidines have been found to be the most active of the series. The biological activity of arylamino- or arylguanidinopyrimidines differs from that of 2,4-diaminopyrimidines in that the former does not competitively reverse the action of folic acid in the growth of S. faecalis . Their inhibitory activity seems to be partially due to their interference with the pyrimidine metabolism of the microorganisms.

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Citations
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Book ChapterDOI
TL;DR: Pyrimidine derivatives have been found to possess fungicidal, antibacterial, antimitotic, antithyroid and surface-anaesthesia activities, with the exception of pyrimidine antibiotics.
Abstract: Publisher Summary The beginning of pyrimidine chemistry may be traced back to the isolation of alloxan, a pyrimidine derivative. The synthesis of barbituric acid from urea and malonic acid perhaps marked the next major event in the development. Since then pyrimidines have occupied a unique and important place in the fields of biological and medicinal chemistry. It is well known that uracil, thymine, and cytosine are essential constituents in nucleic acids; thiamine that possesses antiberiberi activity was the first vitamin discovered in the B series; barbiturates are widely used as sedatives; pyrimethamine is highly potent against erythrocytic parasites in antimalarial study; aminometradine (Mictine) is an orally effective diuretic; and the 5-halogen-substituted uracils and derivatives have recently been reported as antitumour or antiviral agents, or both. Other pyrimidine derivatives have been found to possess fungicidal, antibacterial, antimitotic, antithyroid and surface-anaesthesia activities. With the exception of pyrimidine antibiotics, in this chapter, pyrimidines are classified based on special structural features and functional groups. The chapter discusses the following areas: 2,4- diaminopyrimidines, halogenated pyrimidines, sulphur-substituted pyrimidines, 2-substituted 4-amino-5-hydroxymethylpyrimidines, pyrimidine sulphonamides and pyrimidine antibiotics.

58 citations

Journal ArticleDOI
TL;DR: A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety at the C4 position were designed, with all compounds exhibiting strong activity against wild‐type HIV‐1.
Abstract: A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety at the C4 position were designed, with all compounds exhibiting strong activity against wild-type HIV-1.A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety at the C4 position were synthesized and evaluated for their in vitro activity against HIV in MT-4 cells. All compounds exhibited strong activity against wild-type HIV-1. The most active compound showed activity against wild-type HIV-1 with an EC(50) value of 2.35 nM and against the double mutant strain (K103N+Y181C) with an EC(50) value of 6.6 microM, with a selectivity index greater than 60 000 against wild-type HIV-1. Additionally, some compounds also showed activity against HIV-2 (EC(50)=5.82 microM).

45 citations

Book ChapterDOI
TL;DR: Pyrimidines containing two ethylenimine functions have also been found to possess anticancer activity, and 2, 4-Bis (aziridinyl)-6-chloropyrimidine (CV, ethymidine, etimidin) significantly inhibits growth of many transplantable mouse and rat tumours.
Abstract: Publisher Summary This chapter lists some pyrimidines of biological and medicinal interest, including 5-hydroxypy rimidines, barbituric acid and its derivatives, aminohydroxypyrimidines, pyrimidine amino acids, and nitro and nitrosopyrimidines. The chapter also discusses pyrimidines containing biological alkylating functions. A large number of derivatives of the original nitrogen mustard and other biological akylating agents, such as ethylenimines and epoxides have been prepared as potential anticancer agents. The chapter further explains that the alkylating agents consist of a carrier and the alkylating group, and that differences in selectivity of action upon the tumour, or ability to reach the site of desired action, with minimum damage to the host, are dependent upon the carrier. The chapter also reviews that some pyrimidines containing two ethylenimine functions have also been found to possess anticancer activity. 2, 4-Bis (aziridinyl)-6-chloropyrimidine (CV, ethymidine, etimidin) significantly inhibits growth of many transplantable mouse and rat tumours.

20 citations

Journal ArticleDOI
TL;DR: Investigation of the mechanism of the inhibitory action of the new N-pyrimidyl compounds in S. faecalis revealed that they acted primarily as folic acid antagonists in a manner consistent with an assumption that they interfere with the enzymatic conversion of folic Acid to 5 N-forrnyl tetrahydrofolic acid.
Abstract: Sixteen new N-pyrimidyl amino acids were obtained by substitution at the C-2, C-4, or C-6 position of 2,4-diarnino-6-methylpyrimidine by ‘aromatic amino acids’ or different earboxylalkylamino groups (i.e. aliphatic amino acid moiety). These compounds were tested for their effect on the growth of Streptococcus faecalis, Lactobacillus arabinosus , and Escherichia coli . The new compounds, 2,4-diamino-5-arylazo-6-methylpyrimidine and six N-(5-arylazo-4-pyrimidyl) amino acids, were also studied. It was found that 2,4-diamino-6-methylpyrimidine inhibited growth of all three microorganisms tested, but substitution at the C-2, C-4, or C-6 position by carboxyalkylamino groups produced compounds with little or no inhibitory effects. The three N-pyrimidyl compounds substituted with aromatic amino acids inhibited growth but were less effective than the parent compound. All the 5-arylazopyrimidines significantly inhibited growth of S. faecalis and, to a lesser extent, L. arabinosus . It was observed that among these compounds the inhibitory activity decreased with increase in the bulk of the amino acid moiety. Investigation of the mechanism of the, inhibitory action of these compounds in S. faecalis revealed that they acted primarily as folic acid antagonists in a manner consistent with an assumption that they interfere with the enzymatic conversion of folic acid to 5 N-forrnyl tetrahydrofolic acid in S. faecalis .

7 citations

Journal ArticleDOI

4 citations


References
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Journal ArticleDOI
TL;DR: Evidence is presented that uracil deoxyriboside, which structurally is the simple demethylated form of thymidine, may indeed be the primary acceptor of the methyl group.
Abstract: Most of the literature dealing with the participation of citrovorum factor and vitamin Blz in the formation and transfer of l-carbon intermediates stresses the donor compounds serine, glycine, and formate as precursors of the 5-methyl group of thymidine (2). Uracil deoxyriboside, first isolated in crystalline form by Dekker and Todd (3) in 1950, is known to arise as a result of the deamination of cytosine at the structural level of polynucleotide or nucleoside (4-7). Uracil deoxyriboside can also be directly synthesized by the enzymatic attachment of the deoxyribosyl group to uracil (5,8-10). In this paper, evidence is presented that uracil deoxyriboside, which structurally is the simple demethylated form of thymidine, may indeed be the primary acceptor of the methyl group.

77 citations