1H-Indole-3-carbaldehyde

New acetylenic metabolites from the toxic mushroom Tricholoma pardinum.[Pubmed:32538156]

Nat Prod Res. 2020 Jun 15:1-8.

Four unprecedented acetylenic alcohols, (Z)-non-7-en-5-yn-1,2,4-triol (1), (Z)-non-7-en-5-yn-1,4-diol (2), (Z)-1,2-dihydroxynon-7-en-5-yn-4-one (3), and (Z)-1-hydroxynon-7-en-5-yn-4-one (4) were isolated from the poisonous mushroom Tricholoma pardinum (Agaricales, Basidiomycota), together with the known compounds 1H-Indole-3-carbaldehyde (5) and 6-hydroxy-1H-Indole-3-carbaldehyde (6). Their structures were determined by NMR and IR spectroscopy, and mass spectrometry. The crude acetone extract of the mushroom showed potent anti-arthropod activity against Tetranychus urticae (Acarinae), a dangerous crop pest.

Mycotoxins from Fusarium proliferatum: new inhibitors of papain-like cysteine proteases.[Pubmed:32189177]

Braz J Microbiol. 2020 Mar 18. pii: 10.1007/s42770-020-00256-7.

Papain-like cysteine proteases (PLCPs) in plants are essential to prevent phytopathogen invasion. In order to search for cysteine protease inhibitors and to investigate compounds that could be associated to pineapple Fusarium disease, a chemistry investigation was performed on Fusarium proliferatum isolated from Ananas comosus (pineapple) and cultivated in Czapek medium. From F. proliferatum extracts, nine secondary metabolites were isolated and characterized by nuclear magnetic resonance spectroscopy and mass spectrometry experiments: beauvericin (1), fusaric acid (2), N-ethyl-3-phenylacetamide (3), N-acetyltryptamine (4), cyclo(L-Val-L-Pro) cyclodipeptide (5), cyclo(L-Leu-L-Pro) cyclodipeptide (6), cyclo(L-Leu-L-Pro) diketopiperazine (7), 2,4-dihydroxypyrimidine (8), and 1H-Indole-3-carbaldehyde (9). Compounds 1, 3, and 6 showed significant inhibition of papain, with IC50 values of 25.3 +/- 1.9, 39.4 +/- 2.5, and 7.4 +/- 0.5 muM, respectively. Compound 1 also showed significant inhibition against human cathepsins V and B with IC50 of 46.0 +/- 3.0 and 6.8 +/- 0.7 muM, respectively. The inhibition of papain by mycotoxins (fusaric acid and beauvericin) may indicate a mechanism of Fusarium in the roles of infection process.

Targeted Isolation of Indole Alkaloids from Streptomyces sp. CT37.[Pubmed:32131464]

Molecules. 2020 Mar 2;25(5). pii: molecules25051108.

Four compounds (1-4) were isolated from the extracts of Streptomyces sp. CT37 using bioassay in conjunction with mass spectrometric molecular networking (MN) driven isolation. Their complete structures were established by high-resolution electrospray ionization mass spectrometry (HR-ESIMS), and 1D and 2D nuclear magnetic resonance (NMR) data. Legonimide 1 was identified as a new alkaloid containing a rare linear imide motif in its structure, while compounds 2-4 were already known and their structures were elucidated as 1H-Indole-3-carbaldehyde, actinopolymorphol B, (2R,3R)-1-phenylbutane-2,3-diol, respectively. The biosynthetic pathways of 1-4 were proposed based on the reported biogenesis of indole alkaloids in literature. Bioactivity tests for 1 and 2 revealed moderate growth inhibition activity against Candida albicans ATCC 10231 with MIC95 values of 21.54 microg/mL and 11.47 microg/mL, respectively.

Synthesis, molecular docking and biological evaluation of 2-(thiophen-2-yl)-1H-indoles as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.[Pubmed:31884145]

Bioorg Chem. 2020 Jan;95:103521.

New 2-(thiophen-2-yl)-1H-indole derivatives bearing hydrophobic substituents at the 3-position were designed, synthesized and evaluated for their inhibition of HIV-1 reverse transcriptase (RT) enzyme. Dialkylphosphites (2a-c) or trialkylphosphites (3a-c) were reacted with 2-(thiophen-2-yl)-1H-Indole-3-carbaldehyde (1) yielding the corresponding alpha-hydroxyphosphonate adducts (7a-7c). The reaction of compound 1 with the ylidenetriphenylphosphoranes (4a-4c) proceeds via Wittig mechanism giving the corresponding ethylenes (E, 8a-c). Compounds 8b,c were equally obtained upon reacting aldehyde 1 with the appropriate dialkylphosphonates 5a,b under the Horner-Wittig reaction conditions. On the other hand, the reaction of aldehyde 1 with diethyl cyanomethylene phosphonate (5c) yielded a mixture of the E-ethylene 10 and the cyanovinyl phosphonate 11. The thioaldehyde 12 was obtained upon refluxing aldehyde 1 with the Lawesson's reagent (LR, 6a) or with the Japanese reagent (JR, 6b) in dry toluene. Upon evaluation of HIV-1 Reverse Transcriptase enzyme inhibition, compound 8b (IC50 = 2.93 nM) exhibited the superior HIV-1 RT inhibition and its potency was about 3-folds that of Efavirenz (IC50 = 6.03 nM). Also, compounds 9a (IC50 = 4.09 nM) and 12 (IC50 = 3.54 nM) showed significantly higher inhibition potency. Moreover, compounds 7b (IC50 = 7.48 nM), and 8a (IC50 = 4.55 nM) showed potency not significantly different from that of Efavirenz. Molecular docking experiments on these potent compounds was in accordance with the in vitro data and confirmed binding of these compounds to the enzyme through ring-stacking and hydrogen bond interactions. According to these results, the new molecules would serve as potent HIV-1 NNRTIs inhibitors.

A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt multiple events in lysosome homeostasis.[Pubmed:30806145]

Autophagy. 2019 Oct;15(10):1694-1718.

High-throughput screening identified 5 chemical analogs (termed the WX8-family) that disrupted 3 events in lysosome homeostasis: (1) lysosome fission via tubulation without preventing homotypic lysosome fusion; (2) trafficking of molecules into lysosomes without altering lysosomal acidity, and (3) heterotypic fusion between lysosomes and autophagosomes. Remarkably, these compounds did not prevent homotypic fusion between lysosomes, despite the fact that homotypic fusion required some of the same machinery essential for heterotypic fusion. These effects varied 400-fold among WX8-family members, were time and concentration dependent, reversible, and resulted primarily from their ability to bind specifically to the PIKFYVE phosphoinositide kinase. The ability of the WX8-family to prevent lysosomes from participating in macroautophagy/autophagy suggested they have therapeutic potential in treating autophagy-dependent diseases. In fact, the most potent family member (WX8) was 100-times more lethal to 'autophagy-addicted' melanoma A375 cells than the lysosomal inhibitors hydroxychloroquine and chloroquine. In contrast, cells that were insensitive to hydroxychloroquine and chloroquine were also insensitive to WX8. Therefore, the WX8-family of PIKFYVE inhibitors provides a basis for developing drugs that could selectively kill autophagy-dependent cancer cells, as well as increasing the effectiveness of established anti-cancer therapies through combinatorial treatments. Abbreviations: ACTB: actin beta; Baf: bafilomycin A1; BECN1: beclin 1; BODIPY: boron-dipyrromethene; BORC: BLOC-1 related complex; BRAF: B-Raf proto-oncogene, serine/threonine kinase; BSA: bovine serum albumin; CTSD: cathepsin D; CQ: chloroquine; DNA: deoxyribonucleic acid; EC50: half maximal effective concentration; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HCQ: hydroxychloroquine; HOPS complex: homotypic fusion and protein sorting complex; Kd: equilibrium binding constant; IC50: half maximal inhibitory concentration; KO: knockout; LAMP1: lysosomal associated membrane protein 1; MAP1LC3A: microtubule associated protein 1 light chain 3 alpha; MES: 2-(N-morpholino)ethanesulphonic acid; MTOR: mechanistic target of rapamycin kinase; muM: micromolar; NDF: 3-methylbenzaldehyde (2,6-dimorpholin-4-ylpyrimidin-4-yl)hydrazine;NEM: N-ethylmaleimide; NSF: N-ethylmaleimide sensitive factor; PBS: phosphate-buffered saline; PIKFYVE: phosphoinositide kinase, FYVE-type zinc finger containing; PIP4K2C: phosphatidylinositol-5-phosphate 4-kinase type 2 gamma; PtdIns3P: phosphatidylinositol 3-phosphate; PtdIns(3,5)P2: phosphatidylinositol 3,5-biphosphate; RFP: red fluorescent protein; RPS6: ribosomal protein S6; RPS6KB1: ribosomal protein S6 kinase B1; SQSTM1: sequestosome 1; TWEEN 20: polysorbate 20; V-ATPase: vacuolar-type H(+)-translocating ATPase; VPS39: VPS39 subunit of HOPS complex; VPS41: VPS41 subunit of HOPS complex; WWL: benzaldehyde [2,6-di(4-morpholinyl)-4-pyrimidinyl]hydrazone; WX8: 1H-Indole-3-carbaldehyde [4-anilino-6-(4-morpholinyl)-1,3,5-triazin-2-yl]hydrazine; XBA: N-(3-chloro-4-fluorophenyl)-4,6-dimorpholino-1,3,5-triazin-2-amine hydrochloride; XB6: N-(4-ethylphenyl)-4,6-dimorpholino-1,3,5-triazin-2-amine hydrochloride.

Cytotoxic Sesterterpenes from Thai Marine Sponge Hyrtios erectus.[Pubmed:30487463]

Mar Drugs. 2018 Nov 28;16(12). pii: md16120474.

Four sesterterpenes, erectusolides B, C, D, and seco-manoalide-25-methyl ether, two 2-furanone derivatives, erectusfuranones A and B, together with thirteen known sesterterpenes, (6Z)-neomanoalide-24-acetate, two diastereomers of 24-O-methylmanoalide, luffariolide B, manoalide, (6E)- and (6Z)-neomanoalide, seco-manoalide, scalarafuran, 12-acetylscalarolide, 12-epi-O-deacetyl-19-deoxyscalarin, 12-epi-scalarin, and 12-O-deacetyl-12-epi-scalarin, three indole alkaloids, 5-hydroxy-1H-Indole-3-carbaldehyde, hyrtiosine A, and variabine B, and one norterpene, cavernosine were isolated from the marine sponge Hyrtios erectus. Their structures were determined by means of spectroscopic methods and the absolute configurations of the asymmetric centers were determined using the modified Mosher's method. The cytotoxic activities for the isolated compounds have been reported.

Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular Docking.[Pubmed:29867500]

Front Pharmacol. 2018 May 15;9:498.

Agrocybe aegerita has long been utilized for promoting diuresis in traditional Chinese medicine (TCM) with a close correlation to hypouricemia. Ethanol (AAE) and water (AAW) extracts of the compound led to a remarkable decrease in serum uric acid levels (SUA) in hyperuricemia mice, approaching that of the normal control. Both AAE and AAW exhibited suppression effects on hepatic xanthine oxidase (XOD) activities and elevation effects on renal OAT1 (organic anion transporter 1). However, only little negative impact was observed on the inner organ functions. The molecular docking was used to screen our in-home compound database for A. aegerita, and four compounds including 2-formyl-3,5-dihydroxybenzyl acetate, 2,4-dihydroxy-6-methylbenzaldehyde, 2-(6-hydroxy-1H-indol-3-yl)acetamide, and 6-hydroxy-1H-Indole-3-carbaldehyde (HHC) were identified as potential active compounds. Their inhibitory mechanism on XOD might be attributed to their localization in the tunnel for the entrance of substrates to XOD active site, preventing the entrance of the substrates. To confirm the activity of the screened compounds experimentally, HHC was selected due to its high ranking and availability. The assaying result suggested the significant inhibitory activity of HHC on XOD. Also, these compounds were predicted to carry good ADME (absorption, distribution, metabolism, and excretion) properties, thereby necessitating further investigation. The current results provided an insight into the hypouricemic effects of macrofungi and their bioactives, which might provide the significant theoretical foundation for identifying and designing novel hypouricemia compounds.

A new indole alkaloid from the traditional Chinese medicine Chansu.[Pubmed:28625094]

J Asian Nat Prod Res. 2018 Jun;20(6):581-585.

A new indole alkaloid N'-formylserotonin (1), along with five known indole alkaloids N'-methylserotonin (2), 5-hydroxy-1H-Indole-3-carbaldehyde (3), N-acetylserotonin (4), 6-hydroxy-1-oxo-3,4-dihydro-beta-carboline (5), and bufoserotoin C (6), were isolated from the water extract of traditional Chinese medicine Chansu. Their structures were elucidated on the basis of spectral analyses. The cytotoxicities of 1-6 against human lung adenocarcinoma epithelial cells A549 were tested using the MTT method. Compound 6 exhibited stronger cytotoxic effect than 5-FU, and 1-5 showed no cytotoxic effects. Bufoserotonin C is one of the cytotoxic components in water-soluble extract of Chansu.

Antibacterial and antibiofilm activities of the metabolites isolated from the culture of the mangrove-derived endophytic fungus Eurotium chevalieri KUFA 0006.[Pubmed:28586721]

Phytochemistry. 2017 Sep;141:86-97.

Five previously undescribed metabolites, including acetylquestinol, two prenylated indole 3-carbaldehyde derivatives, an anthranilic acid derivative and an isochromone derivative, were isolated, in addition to eleven known compounds: palmitic acid, ergosterol 5,8-endoperoxide, emodin, physcion, questin, questinol, (11S, 14R)-cyclo(tryptophylvalyl), preechinulin, neoechinulin E, echinulin and eurocristatine, from the culture of the endophytic fungus Eurotium chevalieri KUFA 0006. The structures of the previously undescribed compounds were established based on an extensive 1D and 2D NMR spectral analysis as well as HRMS and IR data. In case of 2-(2, 2-dimethylcyclopropyl)-1H-Indole-3-carbaldehyde and 6, 8-dihydroxy-3-(2S-hydroxypropyl)-7-methylisochromone, the absolute configurations of their stereogenic carbons were established based on comparison of their experimental and calculated ECD spectra. All the compounds, except for palmitic acid and ergosterol 5, 8-endoperoxide, were evaluated for their antibacterial and antibiofilm activities against two Gram-positive and two Gram-negative bacteria, as well as multidrug-resistant isolates from the environment. Emodin not only exhibited moderate antibacterial activity against the Gram-positive bacteria but also showed strong synergistic association with oxacillin against MRSA Staphylococcus aureus.

Biotransformation of isofraxetin-6-O-beta-d-glucopyranoside by Angelica sinensis (Oliv.) Diels callus.[Pubmed:27919656]

Bioorg Med Chem Lett. 2017 Jan 15;27(2):248-253.

Isofraxetin-6-O-beta-d-glucopyranoside, identified from traditional medicinal herbal Xanthoceras sorbifolia Bunge, has been demonstrated to be a natural neuroinflammatory inhibitor. In order to obtain more derivatives with potential anti-neuroinflammatory effects, biotransformation was carried out. According to the characteristics of coumarin skeleton, suspension cultures of Angelica sinensis (Oliv.) Diels callus (A. sinensis callus) were employed because of the presence of diverse phenylpropanoids biosynthetic enzymes. As a result, 15 products were yielded from the suspension cultures, including a new coumarin: 8'-dehydroxymethyl cleomiscosin A (1), together with 14 known compounds. Their structures were elucidated by extensive spectroscopic analysis. Furthermore, the biotransformed pathways were discussed. Among them, compound 13 was transformed from isofraxetin-6-O-beta-d-glucopyranoside, while compounds 1-6, 10-12, 14-15 were derived from the culture medium stimulated by the substrate. The biotransformation processes include hydroxylation, oxidation and esterification. Furthermore, their inhibitory effects on lipopolysaccharide (LPS)-activated nitric oxide (NO) production were evaluated in BV2 microglial cells. It is worth noting that, 1, 1'-methanediylbis(4-methoxybenzene) (3), obtucarbamates A (5), 2-nonyl-4-hydroxyquinoline N-oxide (10) and 1H-Indole-3-carbaldehyde (11) exhibited significant inhibitory effect against neuroinflammation with IC50 values at 1.22, 10.57, 1.02 and 0.76muM respectively, much stronger than that of the positive control minocycline (IC50 35.82muM).

Photochemical synthesis and anticancer activity of barbituric acid, thiobarbituric acid, thiosemicarbazide, and isoniazid linked to 2-phenyl indole derivatives.[Pubmed:27118996]

J Chem Biol. 2015 Nov 17;9(2):57-63.

2-Phenyl-1H-Indole-3-carbaldehyde-based barbituric acid, thiobarbituric acid, thiosemicarbazide, isoniazid, and malononitrile derivatives were synthesized under photochemical conditions. The antitumor activities of the synthesized compounds were evaluated on three different human cancer cell lines representing prostate cancer cell line DU145, Dwivedi (DWD) cancer cell lines, and breast cancer cell line MCF7. All the screened compounds possessed moderate anticancer activity, and out of all the screened compounds, 5-{1[2-(4-chloro-phenyl)2-oxo-ethyl]-2-phenyl-1H-indole-3-ylmethylene}-2-thioxo-d ihydro-pyrimidine-4,6-dione (2b) and 5-{1[2-(4-methoxy-phenyl)2-oxo-ethyl]-2-phenyl-1H-indole-3-ylmethylene}-2-thioxo- dihydro-pyrimidine-4,6-dione (2d) exhibited marked antitumor activity against used cell lines. Additionally, barbituric acid derivatives were selective to inhibit cell line DWD and breast cancer cell lines.

A New Biphenyl Neolignan from Leaves of Patrinia villosa (Thunb.) Juss.[Pubmed:27019553]

Pharmacogn Mag. 2016 Jan-Mar;12(45):1-3.

RESULTS: One new stereoisomer of biphenylneolignan with four known compounds was isolated from the leaves of Patrinia villosa Juss. METHODS: The structure of the new compound was elucidated as 2,6,2',6'-tetramethoxy-4,4'-bis (1,2-trans-2,3-epoxy-1-hydroxypropyl) biphenyl (1) on the basis of spectroscopic analysis and comparison with literature data. The four known compounds were identified as 2,6,2',6'-tetramethoxy-4,4'-bis(1,2-cis-2,3-epoxy-1-hydroxypropyl)biphenyl (2), 1H-Indole-3-carbaldehyde (3), luteolin (4) and quercetin(5) by comparison of their spectral data with the reported data, respectively. CONCLUSIONS: Compound 1 is a new biphenylneolignan, compound 2 and 3 were isolated for the first time from the plant. SUMMARY: One new stereoisomer of biphenylneolignan named 2,6,2',6'-tetramethoxy-4,4'-bis (1,2-trans-2,3-epoxy-1-hydroxypropyl) biphenyl with four known compounds was isolated from the leaves of Patrinia villosa Juss.

Palladacycles of unsymmetrical (N,C(-),E) (E = S/Se) pincers based on indole: their synthesis, structure and application in the catalysis of Heck coupling and allylation of aldehydes.[Pubmed:26974046]

Dalton Trans. 2016 Apr 21;45(15):6718-25.

Unsymmetrical (N,C,E)-type pincer ligand precursors [ and : E = S/Se] with an indole core were synthesized for the first time by the condensation of 1-(2-phenylsulfanyl/selenylethyl)-1H-Indole-3-carbaldehyde with benzyl amine. The synthetic protocols are easy and give good yields (>85%). and on reaction with sodium tetrachloropalladate(ii) in the presence of CH3COONa result in complexes [Pd(/-H)Cl] (/), where they bind in a tridentate (N,C(-),E) mode. and , their aldehyde precursors and Pd(ii)-complexes, and , have been characterized by (1)H, (13)C{(1)H} and (77)Se{(1)H} NMR and HR-MS. Palladium(ii) complexes and and precursor aldehydes of and were verified using single crystal X-ray diffraction. The catalytic activities of complexes and were investigated for Heck coupling and allylation of aldehydes. The two reactions require 0.1-0.3 and 1 mol% loading of complexes as catalysts, respectively.

[Chemical Constituents from Sphagneticola trilobata].[Pubmed:26946839]

Zhong Yao Cai. 2015 Jul;38(7):1426-9.

OBJECTIVE: To study the chemical constituents of the whole plant of Sphagneticola trilobata. METHODS: The compounds were isolated and purified by column chromatography and their structures were determined by spectroscopic techniques. RESULTS: Three lignans, two indolics and two phenolic glycosides were isolated from the whole plant of Sphagneticola trilobata and identified as syringaresinol-4-O-beta-D-glucopyranoside(1), pinoresinol-4-sulfate(2), pinoresinol-4-O-beta-D-glucopyranoside(3), 1H-indole-3-carboxylic acid (4), 1H-Indole-3-carbaldehyde(5), 2,6-dimethoxy-4-hydroxyphenol-1-O-beta-D-glucopyranoside (6), and 3,5-dimethoxy-4-hydroxyphenol-1-O-beta-D-glucopyranoside (7). CONCLUSION: Compounds 1 - 7 are isolated from the genus Wedelia for the first time. Compound 4 demonstrates significant inhibitory activity against alpha-glucosidase.