Synthesis and antiparasitic activity vs T. cruzi and L. donovani of a series of 9-thioaryl acridines are reported. A convenient correlation between molecular structure and biological activity is proposed. Results not only agree with the classical interactions of acridines with DNA but also suggest possible role of charge transfer complexes.

Acridines↗

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Quantitative analysis of structure-activity relationship in the acridine series. Part 2: Antitumor 9-thiadiazolo-acridine derivatives.

Synthesis and activity, vs. leukaemia cells of new 9-thiadiazolo acridine derivatives are reported. In addition, electronic properties and molecular structure are correlated with biological activity of these molecules. Results are in agreement with the capability of drugs to intercalate into DNA.

Acridines↗

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[Soluble proteins of watermelon seeds (Citrullus vulgaria Schr.)].

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Chemical Precipitation↗

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Effects of amino and imino acridines on tumor necrosis factor production by human leukocytes.

Tumor necrosis factor (TNF) is a multifunctional cytokine with diverse effects on different cells and tissues. The biological activity of TNF is described on the basis of its cytotoxic action in vivo and in vitro. Different acridines were systematically synthesized and their effects were tested on endotoxin and Staphylococcus aureus-induced TNF production by human leukocytes. 9-aminobutylacridine and 9-ethylaminoacridine totally abrogated the TNF production of leucocytes at a concentration of 3.5 microM, whereas 9-imino -10-butylacridine and 9-imino-10-ethylacridine exerted only a 50% inhibition in the same concentration. Derivatives designated as 9-amino-(2-dimethylamino-ethyl)-acridine and 9-imino-10-(2-dimethylamino-ethyl)-acridine in a concentration of 7 microM exerted only a 30% and a 10% inhibition respectively. A significant modulation of TNF production was not observed when other alkylated derivatives in this series were applied. The TNF-mediated cytotoxic effect of monocytes against WEHI cells was also reduced by the most effective compounds. The acridines did not interfere with the expression of CD 14 molecules on monocytes. The exact mechanism of the suppression of TNF synthesis by acridines remains to be elucidated, but might be useful in the screening and evaluation of their anticancer properties and antimalarial effects.

Acridines↗

PubMedDate not supplied

Effects of acridines on bacterial plasmid replication and endotoxin.

Different amino- and imino-acridines were systematically synthesized. The antibacterial, antiplasmid, antimotility and endotoxin complexing effect of acridines were studied, when antibacterial effect of the compounds was compared on E. coli. Aminoderivatives were more active than imino-acridines. The N-heptyl-9-imino-acridine was able to select lon minus mutants in the E. coli culture, however, the other acridines tested were ineffective in this respect. The iminoacridines inhibited the motility of Proteus vulgaris more effectively than aminoderivatives. The antimotility action of the acridines was also dependent on the ionic content of the media. The antiplasmid effect was measured on an F-prime plasmid of E. coli LE140 strain. Iminoacridines had a more powerful antiplasmid effect than the amino-substituted derivatives. The majority of the compounds inhibited the intercellular plasmid transfer from E. coli. Kmr donor to a Na-azide resistant recipient. In this test the aminosubstituted derivatives were shown to be more effective inhibitors of conjugation than the imino-substituted compounds. Endotoxin formed complexes with N-butylamino. N-propy-lamino and imidoderivatives. However, complex formation of N-ethyl-, N-heptyl-, N-diethylaminoethyl- and N-diethylamino-propyl-acridines were different. Correlations between molecular orbitals and the antibacterial effects are also discussed.

Acridines↗

PubMedDate not supplied

Effect of acridine derivatives on the multiplication of herpes simplex virus.

The antiviral effect of 22 acridine derivatives was studied on the multiplication of herpes simplex virus type 2 (HSV-2) in Vero cells. The inhibitory effect of four acridine derivatives on the multiplication of HSV-2 is emphasised, six other compounds have moderate activity and three only slightly affect the virus multiplication, while nine compounds are inactive. Some of the effective derivatives inhibit the virus replication without any direct effect on the virus particles. However, the mechanism of the antiviral effect is still not known.

Acridines↗

PubMedDate not supplied

Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression.

We studied the effect of thioacridine derivatives on the function of P-glycoprotein in MDR mouse T-lymphoma cell line L5178 and in MDR human leukemia cell line K562/ADR by rhodamine 123 uptake assay. The effect of some selected thioacridines was also investigated on the expression of the mdr1 gene. Expression was analysed by RT-PCR. Two compounds: 3-amino-9-thio-(4'-nitrobenzyl)acridinone and 2,7-dimethoxy-9-thio-(2'-diethylaminoethyl) acridinone were able to block the function of the P-gp, and also to decrease significantly mdr1 gene expression. Because these two derivatives exert their positive effects as reversing agents they could be potential candidate anticancer agents for further investigation. The thioacridines, which do not affect P-gp function, do not affect or increase the expression of mdr1 gene. Our results showed the structure-activity relationships of these compounds, providing a direction for the development of new, more active compounds.

ATP Binding Cassette Transporter, Subfamily B, Mem↗