- Cellular Stress Upregulates Indole Signaling Metabolites in Escherichia coli
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Kim, Li, et al. describe the characterization of cellular stress-induced, bacterial indole-functionalized metabolites termed “indolokines.” The indolokines are found in diverse bacteria, enhance persister formation in E. coli, and activate innate immune responses in both plant and human tissues.Escherichia coli broadly colonize the intestinal tract of humans and produce a variety of small molecule signals. However, many of these small molecules remain unknown. Here, we describe a family of widely distributed bacterial metabolites termed the “indolokines.” In E. coli, the indolokines are upregulated in response to a redox stressor via aspC and tyrB transaminases. Although indolokine 1 represents a previously unreported metabolite, four of the indolokines (2–5) were previously shown to be derived from indole-3-carbonyl nitrile (ICN) in the plant pathogen defense response. We show that the indolokines are produced in a convergent evolutionary manner relative to plants, enhance E. coli persister cell formation, outperform ICN protection in an Arabidopsis thaliana-Pseudomonas syringae infection model, trigger a hallmark plant innate immune response, and activate distinct immunological responses in primary human tissues. Our molecular studies link a family of cellular stress-induced metabolites to defensive responses across bacteria, plants, and humans.
- Kim, Chung Sub,Li, Jhe-Hao,Barco, Brenden,Park, Hyun Bong,Gatsios, Alexandra,Damania, Ashiti,Wang, Rurun,Wyche, Thomas P.,Piizzi, Grazia,Clay, Nicole K.,Crawford, Jason M.
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- INDOLE COMPOUNDS AND THEIR USE
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The present disclosure relates to indole compounds and pharmaceutical compositions thereof, and their use in stimulating the immune system of patients in need thereof and in treating cancer.
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Paragraph 00191; 00443; 00444
(2019/06/05)
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- Optimization, Structure-Activity Relationship, and Mode of Action of Nortopsentin Analogues Containing Thiazole and Oxazole Moieties
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Plant diseases seriously endanger plant health, and it is very difficult to control them. A series of nortopsentin analogues were designed, synthesized, and evaluated for their antiviral activities and fungicidal activities. Most of these compounds displayed higher antiviral activities than ribavirin. Compounds 1d, 1e, and 12a, with excellent antiviral activities, emerged as novel antiviral lead compounds, among which 1e was selected for further antiviral mechanism research. The mechanism research results indicated that these compounds may play an antiviral role by aggregating viral particles to prevent their movement in plants. Further fungicidal activity tests revealed that nortopsentin analogues displayed broad-spectrum fungicidal activities. Compounds 2p and 2f displayed higher antifungal activities against Alternaria solani than the commercial fungicides carbendazim and chlorothalonil. Current research has laid a foundation for the application of nortopsentin analogues in plant protection.
- Guo, Jincheng,Hao, Yanan,Ji, Xiaofei,Wang, Ziwen,Liu, Yuxiu,Ma, Dejun,Li, Yongqiang,Pang, Huailin,Ni, Jueping,Wang, Qingmin
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p. 10018 - 10031
(2019/10/05)
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- INDOLE AHR INHIBITORS AND USES THEREOF
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The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
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Paragraph 00826; 00829
(2018/11/22)
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- The potential of achiral sponge-derived and synthetic bromoindoles as selective cytotoxins against PANC-1 tumor cells
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Our quest to isolate and characterize natural products with in vitro solid tumor selectivity is driven by access to repositories of Indo-Pacific sponge extracts. In this project an extract of a species of Haplosclerida sponge obtained from the US NCI Natural Products Repository displayed, by in vitro disk diffusion assay (DDA) and IC50 determinations, selective cytotoxicity with modest potency to a human pancreatic cancer cell line (PANC-1) relative to the human lymphoblast leukemia cell line (CCRF-CEM). Two brominated indoles, the known 6-bromo conicamin (1) and the new derivative, 6-Br-8-keto-conicamin A (2), were identified and 2 (IC50 1.5 μM for the natural product vs 4.1 μM for the synthetic material) was determined to be responsible for the cytotoxic activity of the extract against the PANC-1 tumor cell line. The new natural product and ten additional analogs were prepared for further SAR testing.
- Lorig-Roach, Nicholas,Hamkins-Indik, Frances,Johnson, Tyler A.,Tenney, Karen,Valeriote, Frederick A.,Crews, Phillip
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p. 217 - 223
(2017/11/30)
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- The dicarbonylation of indoles: Via Friedel-Crafts reaction with dicarbonyl nitrile generated in situ and retro-cyanohydrination
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A novel one-pot tandem reaction of indole and β-carbonyl nitrile to generate dicarbonyl indoles has been developed. This tandem process involves α-oxonation of the β-carbonyl nitrile to afford α,β-dicarbonyl nitrile, Friedel-Crafts reaction with indoles and subsequent retro-cyanohydrination of cyano tertiary alcohol form dicarbonyl indoles.
- Yan, Jianwei,He, Guangjie,Yan, Fulin,Zhang, Jixia,Zhang, Guisheng
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p. 44029 - 44033
(2016/06/09)
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- BIS-INDOLE ALKALOIDS FOR USE IN THE TREATMENT OF INFECTIONS
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The present application describes bisindole alkaloids of formulas I and II and pharmaceutical compositions thereof useful in the treatment of bacterial infection such as Staphylococcus aureus (MRSA) infection: wherein X1 is: wherein X2 is:
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Page/Page column 39; 40; 44
(2016/02/29)
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- EFFICIENT AND SCALABLE SYSTHESIS OF 2-(1'H-INDOLE-3'-CARBONYL)-THIAZOLE-4-CARBOXYLIC ACID METHYL ESTER AND ITS STRUCTURAL ANALOGS
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Methods of synthesizing 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and structural analogs thereof. The methods include condensation reactions or condensation and oxidation reactions to form the thiazoline or thiazole moiety of ITE or its structural analogs.
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Page/Page column 20-21
(2016/06/01)
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- A new synthesis of versatile indolyl-3-carbonylnitriles
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Abstract Indolyl-3-carbonylnitriles are compounds with demonstrated utility as intermediates in organic chemistry. However, their synthesis remains a challenge, requiring the use of toxic sources of cyanide, and often proceeding in low yields. Accordingly, presented here is a new synthesis of these versatile reactants, via dehydration of easily accessible α-oxoacetamides in generally high yields under simple reaction conditions.
- Veale, Clinton G.L.
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p. 5287 - 5290
(2015/08/26)
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- Methods for making bis-heterocyclic alkaloids
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Methods for making bis-heterocyclic compounds, especially bis-heterocyclic compounds having five and six-membered heterocyclic linkers are described. Also described are methods for making an alpha amino ketone synthon that enables facile syntheses of bisindole compounds, including topsentins and dragmacidins.
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Page column 0095
(2010/11/30)
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- Synthesis of the marine alkaloids rhopaladins A, B, C and D
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The total synthesis of all four known rhopaladins, A-D, isolated from the Okinawan marine tunicate Rhopalaea sp., in two synthetic steps is described, involving an imidate based cyclization with tryptophan esters as the key step to afford the appropriately substituted imidazolinone unit. A short and efficient new synthesis of indol-3-yl-carbonyl nitriles from indol-3-yl-carboxaldehydes and trimethylsilyl cyanide, followed by oxidation with DDQ is also described.
- Janosik, Tomasz,Johnson, Ann-Louise,Bergman, Jan
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p. 2813 - 2819
(2007/10/03)
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- A concise synthesis of topsentin A and nortopsentins B and D.
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[reaction: see text] A concise synthesis of topsentin A (R(1) = R(2) = H) and nortopsentins B (R(1) = Br, R(2) = H) and D (R(1) = R(2) = H) is described from oxotryptamine 5 via reduction of acyl cyanide 4. Regiospecific bromination of 3-cyanoindole afforded 6-bromo-3-cyanoindole (10) as the major product.
- Miyake,Yakushijin,Horne
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p. 2121 - 2123
(2007/10/03)
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