Detail of "53-85-0"

Reference

Inhibition of mammalian DNA replication by dichlorobenzimidazole riboside

Inhibition of mammalian DNA replication by dichlorobenzimidazole riboside. Hand, R.; Tamm, I. (Dep. Med., McGill Univ., Montreal, Que., Can.). Exp. Cell Res., 107(2), 343-54 (English) 1977. CODEN: ECREAL. DOCUMENT TYPE: Journal CA Section: 3 (Biochemical Interactions) In the L-929 line of mouse fibroblasts, the nucleoside analog 5,6-dichloro-1-.beta.-D-ribofuranosylbenzimidazole (I) [53-85-0] (60-75 .mu.M) decreased the rate of nuclear heterogeneous RNA synthesis by 66% and prevented the appearance in the cytoplasm of almost all poly(A)-contg. messenger RNA. At similar dose levels, I inhibited the overall rate of DNA synthesis as measured by thymidine [50-89-5] incorporation by only 20% (after correction for decreased thymidine uptake into total cellular material). Anal. of d. gradients of bromodeoxyuridine and thymidine-3H-substituted DNA and of autoradiograms of extended fibers of thymidine-3H-labeled DNA confirm this inhibition and suggest that I acts on DNA solely by reducing the rate of replication fork movement. The apparent size of replication units was unchanged by drug treatment. I also competitively inhibited the transport of thymidine into cells. Several other aspects of thymidine metab. were not affected by I.

A comparative study of the effects of certain halogenated benzimidazole ribosides on RNA synthesis, cell proliferation, and interferon production

A comparative study of the effects of certain halogenated benzimidazole ribosides on RNA synthesis, cell proliferation, and interferon production. Tamm, Igor; Sehgal, Pravinkumar B. (Rockefeller Univ., New York, N. Y., USA). J. Exp. Med., 145(2), 344-56 (English) 1977. CODEN: JEMEAV. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) 5-(Or 6-)Bromo-4,5-(or 5,7-)dichloro-1-.beta.-D-ribofuranosylbenzimidazole, 5,6-dibromo-1-.beta.-D-ribofuranosylbenzimidazole [62299-24-5], and 5,6-dichloro-1-.beta.-D-ribofuranosyl-benzimidazole (I) [53-85-0] show closely similar structure-activity relations with respect to inhibition of cellular RNA synthesis, inhibition of cellular proliferation, and enhancement of interferon prodn. The activities of these compds. are ranked .5:1. The log dose-response curves constructed for inhibition of FS-4 cell RNA synthesis show similar slopes and a leveling off at 60-70% inhibition of RNA synthesis at the highest concns. of each compd. tested. This suggests that these 3 derivs. act through the same mechanism. The concns. of the benzimidazole ribosides at which the rate of proliferation of human fibroblasts (FS-4) is reduced by 50% are as follows: monobromodichloro: 1.7 .mu.M (0.68 .mu.g/mL); dibromo: 12 .mu.M (4.9 .mu.g/mL); dichloro: 38 .mu.M (12 .mu. 62299-25-6 and 51-17-2 which are cas registry numbers of substances are two of reagents here.g/mL). All compds. reduce the exponential rate of cell proliferation in a dose-dependent manner. The inhibition of cell growth is reversible on removal of the compds. from the medium. Protocols based on any 1 of the 3 halobenzimidazole ribosides give interferon yields from poly(I).cntdot.poly(C)-induced FS-4 cells which are comparable to the high yields obtained with the conventional cycloheximide-actinomycin D protocol. The enhancement of interferon yield depends on blocking of the synthesis of RNA which is involved in the shutoff of interferon prodn. .