19194-62-8Relevant articles and documents
Cellular Stress Upregulates Indole Signaling Metabolites in Escherichia coli
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.
, p. 698 - 7,707 (2020)
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.
Optimization, Structure-Activity Relationship, and Mode of Action of Nortopsentin Analogues Containing Thiazole and Oxazole Moieties
Guo, Jincheng,Hao, Yanan,Ji, Xiaofei,Wang, Ziwen,Liu, Yuxiu,Ma, Dejun,Li, Yongqiang,Pang, Huailin,Ni, Jueping,Wang, Qingmin
, p. 10018 - 10031 (2019/10/05)
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.
The potential of achiral sponge-derived and synthetic bromoindoles as selective cytotoxins against PANC-1 tumor cells
Lorig-Roach, Nicholas,Hamkins-Indik, Frances,Johnson, Tyler A.,Tenney, Karen,Valeriote, Frederick A.,Crews, Phillip
, p. 217 - 223 (2017/11/30)
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.
