Hurley, L. H. (1979). Pyrrolo[1,4]benzodiazepine antibiotics. Biosynthesis of the antitumor antibiotic sibiromycin by streptosporangium sibiricum. Biochemistry, 18(19), 4225-4229.
PMID: 582800;Abstract:
The biosynthesis of the antitumor antibiotic sibiromycin by Streptosporangium sibiricum requires the construction of four units: the amino sugar from glucose; the anthranilate ring from DL-tryptophan probably via kynurenine; the aromatic methyl group from methionine; the propylidene proline from L-tyrosine with the loss of two aromatic carbons and addition of a C-1 from methionine. Retention of tritium from DL-[5-3H]tryptophan in sibiromycin suggests an NIH shift during hydroxylation of an intermediate. © 1979 American Chemical Society.
Hurley, L. H., & Gairola, C. (1979). Pyrrolo (1,4) benzodiazepine antitumor antibiotics: Biosynthetic studies on the conversion of tryptophan to the anthranilic acid moieties of sibiromycin and tomaymycin. Antimicrobial Agents and Chemotherapy, 15(1), 42-45.
PMID: 581831;PMCID: PMC352597;Abstract:
Biosynthetic intermediates between tryptophan and the anthranilate mioeties of tomaymycin and sibiromycin have been suggested, based upon a combination of feeding experiments with either carbon-14-labeled substrates or competition experiments between radiolabeled tryptophan and unlabeled intermediates. In the case of sibiromycin and tomaymycin, substitution of the aromatic ring most likely takes place at the kynurenine stage. Feeding experiments with the antramycin culture were inconclusive, most likely because of the cell impermeability.
Reynolds, V. L., McGovren, J. P., & Hurley, L. H. (1986). The chemistry, mechanism of action and biological properties of CC-1065, a potent antitumor antibiotic. Journal of Antibiotics, 39(3), 319-334.
Hurley, L. H., Gairola, C., & Zmijewski Jr., M. J. (1975). Biosynthesis of the antiviral antibiotic 11-demethyltomaymycin by Streptomyces achromogenes. Journal of the Chemical Society, Chemical Communications, 120-121.
Abstract:
The building blocks for 11-demethyltomay-mycin have been established as trytophan, tyrosine and a one carbon unit via methionine.
V., P., Hahn, S., Beman, C., Biswanath, D. e., Brooks, T. A., Gokhale, V., & Hurley, L. H. (2012). Anticancer activity and cellular repression of c-MYC by the G-quadruplex-stabilizing 11-piperazinylquindoline is not dependent on direct targeting of the G-quadruplex in the c-MYC promoter. Journal of Medicinal Chemistry, 55(13), 6076-6086.
PMID: 22691117;PMCID: PMC3395776;Abstract:
This G-rich region of the c-MYC promoter has been shown to form a G-quadruplex structure that acts as a silencer element for c-MYC transcriptional control. In the present work, we have synthesized a series of 11-substituted quindoline analogues as c-MYC G-quadruplex-stabilizing compounds, and the cell-free and in vitro activity of these compounds were evaluated. Two lead compounds (4 and 12) demonstrated good cell-free profiles, and compound 4 (2-(4-(10H-indolo[3,2-b]quinolin-11-yl)piperazin-1-yl)-N,N-dimethylethanamine) significantly down-regulated c-MYC expression. However, despite the good cell-free activity and the effect of these compounds on c-MYC gene expression, we have demonstrated, using a cellular assay in a Burkitts lymphoma cell line (CA46-specific), that these effects were not mediated through targeting of the c-MYC G-quadruplex. Thus, caution should be used in assigning the effects of G-quadruplex-interactive compounds that lower c-MYC to direct targeting of these promoter elements unless this assay, or similar ones, demonstrates direct targeting of the G-quadruplex in cells. © 2012 American Chemical Society.
