[Gamma-glutamyltransferase (EC 2.3.2.2) activity in the course of brachytherapy of the uterine cervix and corpus carcinoma]. / Aktywnosc gamma-glutamylotransferazy (EC 2.3.2.2) w monitorowaniu brachyterapii raka szyjki i trzonu macicy.

The gamma-glutamyltransferase (EC 2.3.2.2) activity was measured in the blood serum obtained from 25 female patients with the uterine cervix carcinoma 10 and from 21 women with the uterine corpus carcinoma 10, treated by brachytherapy. The enzyme activity was determined in the five time points: before the brachytherapy, in the middle of the treating course, immediately after the application of the full dose of radium and in the seventh and the fourteenth day after the finishing the treatment. It was assumed the changes in the enzyme activity during the treatment course, and the highest values were observed immediately after the brachytherapy. It was noticed, that there is the direct connection between the enzyme activity changes and used brachytherapy method.

Synthesis and antiviral activity of novel isonucleoside analogs.

A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3 alpha, 4 beta, 5 alpha)]-2-amino-1, 9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereospecifically achieved starting from 1,2-isopropylidene-D-xylofuranose (10). An efficient two-step reduction of the anomeric center of bis-acetate 18 involved formation of the chloride intermediate 19, followed by diisobutylaluminum hydride reduction. Tosylation of the resulting alcohol 20 provided the key intermediate 21, which was coupled with a variety of nucleobase anions. Several members of this new class of compounds possess activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). Compound 7 exhibits potent and selective activity against thymidine kinase encoding herpesviruses, in particular, HSV-1 and HSV-2. Evaluation of compound 7 for inhibition of WI-38 cell growth indicated an ID50 of > 700 microM. Although the antiherpetic activity in vitro of 7 is less than that of acyclovir (1), compound 7 displays superior efficacy in mouse model infections. The (bromovinyl)uridine analog 8 (BMS-181,165) also exhibits selective activity against HSV-1 and VZV, with no cytostatic effect on WI-38 cell growth at > 800 microM. Compound 8 is active against simian varicella virus and is efficacious in the corresponding monkey model.

Evaluation of SQ 34,514: pharmacokinetics and efficacy in experimental herpesvirus infections in mice.

The new antiviral nucleoside SQ 34,514 [(1R-1 alpha, 2 beta, 3 alpha)-2-amino-9- [2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one], the active R isomer of racemic SQ 33,054 (cyclobut-G), was evaluated for efficacy in the treatment of herpesvirus infections in mice. SQ 34,514 was orally efficacious in a herpes simplex virus type 1 (HSV-1) systemic infection, an intracerebral HSV-2 infection, a vaginally induced HSV-2 infection in ovariectomized mice, and in a systemic murine cytomegalovirus infection. SQ 34,514 compared favorably with acyclovir and ganciclovir in the treatment of these experimental infections. In mice, SQ 34,514 had an oral bioavailability of 80% based on urinary excretion. SQ 34,514 may have potential value in the therapy of HSV and cytomegalovirus infections in humans.