Reverse transcriptase inhibition

Mashino T, Shimotohno K, Ikegami N, Nishikawa D, Okuda K, Takahashi K, Nakamura S, Mochizuki M (2005) Human immunodeficiency virus-reverse transcriptase inhibition and... 

Gussio, R., Pattabieaman, N., Kellogg, G.E., Zahaeevitz, D.W. Use of 3D QSAR methodology for data mining the National Cancer Institute Repository of Small Molecules application to HlV-1 reverse transcriptase inhibition. Methods 1998, 14, 255-263. 

Reverse transcriptase inhibition. Decoction of the rhizome, in cell culture, was active on Rauscher murine leukemia virus. The study was conducted with a prescription consisted of Bupleurum falcatum (Rt), Scutellaria baicalensis (Rt), Pinellia ternata (Tu), Zizyphus jujuba (Fr), Panax ginseng (Rt), and Glycyrrhiza glabra (Rh) h Serotonin antagonist activity. Acetone extract of the rhizome, at a concentration of 25 pg/mL, was active on the guinea pig ileum vs serotonin-induced contract-ions ° . 

Chen, H. and Gold, L. (1994) Selection of high-affinity RNA ligands to reverse transcriptase inhibition of cDNA synthesis and RNase H activity. Biochemistry, 33, 8746-8756. 

H. Nakashima, Y. Kido, N. Kobayashi, Y. Motoki, M. Neushul, and N. Yamamoto, Antiretroviral activity in a marine algae Reverse transcriptase inhibition by an aqueous extract of Schizymenia pacifica, J. Cancer Res. Clin. Oncol., 113 (1987) 413 416. 

Tramontane, E. Cheng, Y. C. HIV-1 reverse transcriptase inhibition by a dipyridodia-zepinone derivative BI-RG-587. Biochem. Pharmacol, 1992, 43 1371-1376. 

As an example, let us consider the MFTA model of the HIV-1 reverse transcriptase inhibition by the tetrahydroimidazobenzodiazepinone (TIBO) derivatives. The model is based on the atomic charge Q, atomic van der Waals radius R and group lipophilicity Lg as the local descriptors (V=73, Np=5, i = 0.887, g = 0.686). Figure 5.5 shows the molecular supergraph with the superimposed structure of one training set compound. 

The most active compound was O-demethylbuchenavianine (15) but this was quite cytotoxic against the lymphoblastoid host cells used in the assay. When tested in other systems using different strains of HIV and different host cells (15) had little effect and it also showed little activity when tested for a variety of activities including reverse-transcriptase inhibition and HIV-1 protease inhibition. In view of the low therapeutic index and only partial protection against HIV infection O-demethylbuchenavianine was not considered suitable for further development. 

The mechanism of actions involves tubulin binding, reverse transcriptase inhibition, integrase inhibition and topoisomerase inhibition. Podophyllo-toxins bind to tubulin and are able to disrupt the cellular cytoskeleton and interfere with some vital virus processes. There is no relationship between the inhibition of reverse transcriptase (RT) and chemical structure in the case of lignans, because all the chemical antiviral structures are able to bind to the enzyme. As to the rest of the mechanism, there is not much information available. The effects of rabdosiin may be due to its topoisomerase inhibitory effects. Charlton concluded that the antiviral activity of lignans is not strong and that except for podophyllotoxin, which is used topically to treat various warts caused by HPV, none of them are of interest for commercial application. 

This type of AZT-enzyme interaction may result in reverse transcriptase inhibition and/or DNA chain-termination [240]. 

Kilkuskie, R.E., Kashiwada, Y, Nonaka, G.-i. et al. (1992). HIV and reverse transcriptase inhibition by tannins. Bioorganic Medicinal Chemistry Letters, 2,1529-1534. 

The second major activity investigated for the ansamycins - reverse transcriptase inhibition - does not follow closely that of bacterial inhibition. Thus, the most active antibacterial rifamycin derivatives are rather... 

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