1912-33-0Relevant academic research and scientific papers
Construction of indole and benzofuran systems on the solid phase via palladium-mediated cyclizations
Zhang, Han-Cheng,Maryanoff, Bruce E.
, p. 1804 - 1809 (1997)
Molecular diversity in the area of nonpeptide, small organic molecules has been receiving considerable attention in the chemical community. Herein, we report new solid-phase methodology for the rapid generation of such small-molecule libraries by simultaneous-parallel or combinatorial synthesis. We have adapted a palladium-mediated, intramolecular Heck-type reaction, a mild and versatile method for carbon-carbon bond formation, to the solid phase. This has been applied to the synthesis of diverse indole and benzofuran derivatives, such as 8, 15, and 28, in good to excellent yields.
Development of a peptidomimetic ligand for efficient isolation and purification of factor VIII via affinity chromatography
Kn?r, Sebastian,Khrenov, Alexey V.,Laufer, Burkhardt,Saenko, Evgueni L.,Hauser, Charlotte A. E.,Kessler, Horst
, p. 4329 - 4339 (2007)
Hemophilia A, one of the most severe bleeding disorders, results from an inherited deficiency of factor VIII (FVIII) function. Treatment by injection of FVIII has been a common procedure for decades. Nevertheless, the production and purification of FVIII remains a challenging task. Current procedures using immunoaffinity chromatography are expensive and suffer from the instability of the applied antibody ligands, which elute along with the product and contaminate it. Recently, FVIII was purified by use of octapeptide ligands, but their low protease-resistance limits their application. We here report the systematic rational and combinatorial optimization procedure that allowed us to transfer the octapeptide ligands into a small peptidomimetic. This compound is the smallest ligand known for separation of such a large protein (330 kDa). It not only binds and purifies FVIII with high efficiency but also is stable, protease-resistant, and cheap to produce in preparative scale. Hence it offers a valuable alternative to antibody-based purification procedures.
Reconsidering the Structure of Serlyticin-A
Tsui, Ka Yi,Tombari, Robert J.,Olson, David E.,Tantillo, Dean J.
, p. 3464 - 3468 (2019)
Serlyticin-A is a secondary metabolite first isolated from a culture of Serratia ureilytica grown using squid pen as the sole carbon/nitrogen source. A previous study by Kuo et al. demonstrated that it has antioxidative and antiproliferative properties. However, the proposed chemical structure of serlyticin-A is likely incorrect based on the thermodynamic instability of its three contiguous heteroatom-heteroatom bonds. Here, we use quantum chemical calculations to predict 1H and 13C chemical shifts for serlyticin-A and demonstrate a discrepancy between the calculated and experimental chemical shifts. We then propose several reasonable alternative structures for serlyticin-A. Considering the known antioxidant and antiproliferative activity of hydroxamic acids as well as their stability and prevalence in natural products of bacterial origin, we believe that serlyticin-A is most likely 3-indolylacetohydroxamic acid (4). We provide our rationale for this assignment as well as experimental data for pure 3-indolylacetohydroxamic acid obtained via de novo synthesis. This study highlights the power of computational NMR shift prediction to revise chemical structures for natural products like serlyticin-A.
Reaction of methyl (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate with ureas: Facile entry into the polycyclic meridianin analogues with uracil structural unit
?asar, Zdenko,Bevk, David,Svete, Jurij,Stanovnik, Branko
, p. 7508 - 7519 (2005)
Methyl (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate was prepared simply and efficiently in two steps from 3-indoleacetic acid employing N,N-dimethylformamide dimethylacetal (DMFDMA). Upon treatment of (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate with various (thio)ureas in the presence of an acid 2-(1H-indol-3-yl)-3-(3-substituted(thio)ureido) propenoates were obtained in high yields. A base promoted cyclization of these (thio)ureidopropenoate derivatives afforded 5-(indol-3-yl)-3-substituted- pyrimidine-2,4-diones which represent a new family of meridianine analogues.
Metabolism of indole-3-acetic acid in rice: Identification and characterization of N-β-d-glucopyranosyl indole-3-acetic acid and its conjugates
Kai, Kenji,Wakasa, Kyo,Miyagawa, Hisashi
, p. 2512 - 2522 (2007)
A search was made for conjugates of indole-3-acetic acid (IAA) in rice (Oryza sativa) using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) in order to elucidate unknown metabolic pathways for IAA. N-β-d-Glucopyranosyl indole-3-acetic acid (IAA-N-Glc) was found in an alkaline hydrolysate of rice extract. A quantitative analysis of 3-week-old rice demonstrated that the total amount of IAA-N-Glc was equal to that of IAA. A LC-ESI-MS/MS-based analysis established that the major part of IAA-N-Glc was present as bound forms with aspartate and glutamate. Their levels were in good agreement with the total amount of IAA-N-Glc during the vegetative growth of rice. Further detailed analysis showed that both conjugates highly accumulated in the root. The free form of IAA-N-Glc accounted for 60% of the total in seeds but could not be detected in the vegetative tissue. An incorporation study using deuterium-labeled compounds showed that the amino acid conjugates of IAA-N-Glc were biosynthesized from IAA-amino acids. IAA-N-Glc and/or its conjugates were also found in extracts of Arabidopsis, Lotus japonicus, and maize, suggesting that N-glucosylation of indole can be the common metabolic pathway of IAA in plants.
QUANTIFICATION OF INDOL-3-YL ACETIC ACID IN PEA AND MAIZE SEEDLINGS BY GAS CHROMATOGRAPHY-MASS SPECTROMETRY
Allen, James R. F.,Rivier, Laurent,Pilet, Paul-Emile
, p. 525 - 530 (1982)
A procedure is described for the identification and quantification of IAA in plant tissues by GC/MS analysis of the N-heptafluorobutyryl ethyl ester of IAA using IAA as an internal standard.The detection limit is ca. 3 pmol IAA/tissue sample.By using this method, IAA levels of 30-90 pmol/g fr. wt were obtained for dark-grown Pisum sativum epicotyls and 71-199 pmol/g fr. wt for dark-grown Zea mays seedlings.When either methanol or ethanol was used as extraction solvent, some esterification of IAA during sample preparation was observed.No evidence for the natural occurence of methyl or ethyl esters of IAA in Pisum sativum seedlings was found.Key Word Index-Pisum sativum; Zea mays; Leguminosae; Gramineae; hormone; indol-2-yl acetic acid; GC/MS; deuterium label.
Marine-inspired bis-indoles possessing antiproliferative activity against breast cancer; design, synthesis, and biological evaluation
Eldehna, Wagdy M.,Hassan, Ghada S.,Al-Rashood, Sara T.,Alkahtani, Hamad M.,Almehizia, Abdulrahman A.,Al-Ansary, Ghada H.
, (2020)
Diverse indoles and bis-indoles extracted from marine sources have been identified as promising anticancer leads. Herein, we designed and synthesized novel bis-indole series 7a-f and 9a-h as Topsentin and Nortopsentin analogs. Our design is based on replacing the heterocyclic spacer in the natural leads by a more flexible hydrazide linker while sparing the two peripheral indole rings. All the synthesized bis-indoles were examined for their antiproliferative action against human breast cancer (MCF-7 and MDA-MB-231) cell lines. The most potent congeners 7e and 9a against MCF-7 cells (IC50 = 0.44 ± 0.01 and 1.28 ± 0.04 μM, respectively) induced apoptosis in MCF-7 cells (23.7-, and 16.8-fold increase in the total apoptosis percentage) as evident by the externalization of plasma membrane phosphatidylserine detected by Annexin V-FITC/PI assay. This evidence was supported by the Bax/Bcl-2 ratio augmentation (18.65- and 11.1-fold compared to control) with a concomitant increase in the level of caspase-3 (11.7- and 9.5-fold) and p53 (15.4- and 11.75-fold). Both compounds arrested the cell cycle mainly in the G2/M phase. Furthermore, 7e and 9a displayed good selectivity toward tumor cells (S.I. = 38.7 and 18.3), upon testing of their cytotoxicity toward non-tumorigenic breast MCF-10A cells. Finally, compounds 7a, 7b, 7d, 7e, and 9a were examined for their plausible CDK2 inhibitory action. The obtained results (% inhibition range: 16%-58%) unveiled incompetence of the target bis-indoles to inhibit CDK2 significantly. Collectively, these results suggested that herein reported bis-indoles are good lead compounds for further optimization and development as potential efficient anti-breast cancer drugs.
Discovery of an indole-substituted furanone with tubulin polymerization inhibition activity
Mowery, Patricia,Filkorn, Madison M.,Hurysz, Brianna,Kwansare, Deborah O.,Lafferty, Megan M.,McFadden, Marissa A.,Neerukonda, Namita D.,Patel, Roslyn R.,Pierce, Kelsey,Sockett, Kaitlynn A.,Truax, Nathanyal J.,Webster, Nathan R.,Pelkey, Erin T.
, (2021)
Analogs of diarylpyrrolinone lead compound 1 were prepared and tested for anti-proliferative activity in U-937 cancer cells. Alterations of 1 focused on modifying the two nitrogen atoms: a) the pyrrolinone nitrogen atom was substituted with a propyl group or replaced with an oxygen atom (furanone), and b) the substituents on the indole nitrogen were varied. These changes led to the discovery of a furanone analog 3b with sub-micromolar anti-cancer potency and tubulin polymerization inhibition activity.
Molecular cloning and biochemical characterization of indole-3-acetic acid methyltransferase from poplar
Zhao, Nan,Guan, Ju,Lin, Hong,Chen, Feng
, p. 1537 - 1544 (2007)
Indole-3-acetic acid (IAA) is the most active endogenous auxin and is involved in various physiological processes in higher plants. Concentrations of IAA in plant tissues are regulated at multiple levels including de novo biosynthesis, conjugation/deconjugation, and degradation. In this paper, we report molecular isolation and biochemical characterization of a gene PtIAMT1 from poplar encoding IAA methyltransferase (IAMT), which plays a role in regulating IAA homeostasis. PtIAMT1 was identified from the poplar genome based on sequence similarity to Arabidopsis IAMT. A full-length cDNA of PtIAMT1 was cloned from poplar roots via RT-PCR. Recombinant PtIAMT1 expressed in Escherichia coli was purified to electrophoretic homogeneity. Enzyme assays combined with GC-MS verified that PtIAMT1 catalyzes formation of methyl indole-3-acetate using S-adenosyl-l-methionine (SAM) as a methyl donor and IAA as a methyl acceptor. PtIAMT1 had a temperature optimum at 25 °C and a pH optimum at pH 7.5. Its activity was promoted by K+ but inhibited by Fe2+, Cu2+ and Zn2+. Under steady-state conditions, PtIAMT1 exhibited apparent Km values of 23.1 μM and 30.4 μM for IAA and SAM, respectively. Gene expression analysis showed that PtIAMT1 had the highest level of expression in stems, a moderate level of expression in young leaves, and a low level of expression in roots. Presence of PtIAMT1 transcripts in several organs suggests that PtIAMT1 is involved in development of multiple organs in poplar.
Etude spectroscopique (IR, RMN1H, masse) comparee des acides indolyl-1 acetique (AIA-1) indolyl-2 acetique (AIA-2) et indolyl-3 acetique (AIA-3) et de leurs esters methyliques (masse)
Vebrel, Joel,Laude, Bernard,Seguin, Alain,Dubouchet, Jacques
, p. 887 - 894 (1983)
Spectroscopic study (i.r., PMR) of 1-indolyl, 2-indolyl and 3-indolyl acetic acids points out structural differences.Conventional mass spectra of the three acids or their methyl esters are very similar.Use of the MIKE and CID-MIKE techniques on the molecular ion allows an easy discrimination of each methylic ester of the three acids.
