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A series of mononuclear Ru(II) complexes of the type [Ru(S)(2)(K)](2+), where S = 1,10-phenanthroline/2,2'-bipyridine and K = 4-OH-btsz, 4-CH(3)-btsz, 3,4-di-OCH(3)-btsz, 4-OH-binh, 4-CH(3)-binh, 3,4-di-OCH(3)-binh, were prepared and characterized by elemental analysis, FTIR, (1)H-NMR, and mass spectroscopy. The complexes displayed metal-ligand charge transfer (MLCT) transitions in the visible region. These ligands formed bidentate octahedral ruthenium complexes. The title complexes were evaluated for their in vivo anticancer activity against a transplantable murine tumor cell line, Ehrlisch's ascites carcinoma (EAC), and in vitro cytotoxic activity against human cancer cell lines Molt 4/C(8) and CEM and murine tumor cell line L1210. The ruthenium complexes showed promising biological activity especially in decreasing tumor volume and viable ascites cell counts. Treatment with these complexes prolonged the life span of mice bearing EAC tumors by 10-52%. In vitro evaluation of these ruthenium complexes revealed cytotoxic activity from 0.21 to 24 muM against Molt 4/C(8), 0.16 to 19 microM against CEM, and 0.75 to 32 microM against L1210.
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Abstract The title compound (IXa) is prepared by reaction of (VI) with the thioimidate (Ic) [obtained in three steps from (II)] to give (VII), followed by treatment with ammonia.
This chapter discusses the Pyran (maleic anhydride divinylether) copolymer and tilorone, 2,7-bis[2-(diethylamino)ethoxy] fluoren-9-one. Following the initial discovery of the interferon inducing properties of pyran copolymer and tilorone, several other synthetic polycarboxylates, related to pyran copolymer, as well as fluorenone ethers, esters, and ketones, related to tilorone, have been described. Various non-nucleotide substances are able to stimulate interferon production in vivo animals and or leukocyte cultures. The spectrum of antiviral activity of poly acrylic acid (PAA) and chlorite-oxidized oxyamylose (COAM) in cell culture has not been analyzed, but the occasional results obtained with PAA and COAM in vitro did not differ markedly from those obtained with polymethacrylic acid PMAA. Thus, Interferon production does not offer a satisfactory explanation for many of the antiviral, antitumoral, and other biological effects demonstrated by polycarboxylates and tilorone in vivo. The observations seem to refute the likelihood that the antiviral, antitumoral, antibacterial, antifungal, and antiprotozoal activities of polycarboxylates and tilorone are mediated by interferon production.
Diazomethane treatment of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) in the presence of SnCl2 as catalyst led to quantitative formation of the 2'-O-methyl and 3'-O-methyl derivatives of the parent compound. The products were successfully fractionated on a basic ion-exchange column and isolated in crystalline form. Indentification was based on the elution sequence from the column and on 1H NMR spectroscopy. Both derivatives were found to be inactive, relative to the parent compound, against several virus types in cell culture. Unlike ribavirin itself, the 2'(3')-O-methyl derivatives did not suppress cellular DNA synthesis. NMR data showed that the loss of biologic activity upon 2'(3')-O-methylation was not due to a change of conformation of the nucleoside sugar moiety.
The antiherpesvirus agent (E)-5-(2-bromovinyl)-2'-deoxyuridine caused marked alterations in the synthesis and processing of several herpes simplex virus type 1 (HSV-1)-infected-cell polypeptides. Analogous to other thymidine analogs, there was a dose-dependent decrease in several beta and gamma polypeptides and an accumulation of HSV-1 thymidine kinase. In contrast to the action of other thymidine analogs, there were alterations in alpha polypeptides, including an increase in the synthesis and phosphorylation of infected-cell polypeptide 4b and a decrease in the synthesis of infected-cell polypeptide 27. The phosphorylation of several other HSV-1 phosphoproteins was mildly inhibited. (E)-5-(2-Bromovinyl)-2'-deoxyuridine inhibited the glycosylation of the major HSV-1 glycoproteins, and this activity appeared to be independent of the incorporation of the drug into the viral DNA. Thus, the alterations in HSV-1 polypeptide expression appear to be due to the presence of the drug in a low-molecular-weight form as well as its presence in the viral DNA. This suggests that this analog or a phosphorylated derivative might act as an inhibitor of an enzyme(s) responsible for posttranslational modification of polypeptides.
3'-Azido-2',3'-dideoxy-6-methyluridine ( VIb ) was prepared, together with its N 3 -isomer VIIb , by opening the 2,3'-bond in anhydronucleoside III with lithium azide in dimethylformamide and subsequent detritylation. The anhydro derivative III was synthesized from 2'-deoxy-6-methyluridine ( I ) by tritylation, mesylation and closure of the 2,3'-anhydro bond with 1,8-diazabicyclo[5.4.0]undec-7-ene. Dideoxy derivative XV was prepared by Barton deoxygenation of phenoxythiocarbonyl derivative IX followed by desilylation with tetrabutylammonium fluoride. Reduction of bis(phenoxythiocarbonyl) derivative XV with tributyltin hydride afforded 2',3'-dideoxy-2',3'-didehydro derivative XVI . The compound XV was obtained from arabinosyl derivative XIII which arises, along with 5,6-dihydro derivative XIV , by reaction of anhydronucleoside XII with lithium hydroxide in aqueous methanol. Desilylation of compound XVI with tetrabutylammonium fluoride resulted in quantitative removal of 6-methyluracil.
