Matches in SemOpenAlex for { <https://semopenalex.org/work/W187443672> ?p ?o ?g. }
- W187443672 endingPage "104" @default.
- W187443672 startingPage "81" @default.
- W187443672 abstract "Ailanthus altissima Swingle (Simaroubaceae) is a medicinal plant used in traditional medicine as an antiviral and an antitumoral drug. Its roots have been successively extracted, at room temperature, with solvents of increasing polarity. The extracts were tested for their antiproliferative activity on HeLa (human cervical carcinoma cell line), at a dose of 10 μg/mL. The chloroform extract, the most active in biological assays, was fractionated on a silica-gel column: the fractions obtained were assayed on the proliferation of the same cellular line, at a dose of 10 mg/mL. The most active fraction (100% of cytotoxic activity) demonstrated to contain a single substance. The identification of this active substance, recognized as 1-methoxy-canthin-6-one, was performed by NMR methods. This indole alkaloid has shown antiproliferative and proapoptotic effects on several tumoral cell lines. In particular, it provoked mitochondrial membrane depolarization, mitochondrial release of cytochrome c and Smac/DIABLO, and caspase 3 activation on Jurkat cells (human leukemia cell line). The compound was active also on other tumor cell lines, HuH7 (hepatocellular carcinoma), NPA (human papillary carcinoma), and ARO (anaplastic thyroid cell line): the apoptosis-inducing activity was evident at a concentration of < 10 μmol/L until half maximal at about 40 μmol/L. Peripheral blood mononuclear cells (PBMC) from healthy subjects have been used as control; in these cells, the alkaloid showed no proapoptotic activity. The effects of 1-methoxy-canthin-6-one, in combination with TRAIL (human recombinant tumor necrosis factor-related apoptosis-inducing ligand), has also been investigated on Jurkat cells using suboptimal concentrations of both agents, showing 45% apoptosis. Also, the TMRE (tetramethylrhodamine ethyl ester) bioassay resulted in a definite mitochondrial membrane depolarization, when alkaloid and TRAIL are used together, always using their suboptimal concentrations. The study of the possible synergism has shown that the alkaloid increases TRAIL R1 receptors, inducing JNK activation and c-Jun phosphorylation. JNK inhibition reduces only partly the synergism between alkaloid and TRAIL; therefore, other factors take part in TRAIL-induced apoptosis, besides TRAIL R1 upregulation. In order to obtain more information about biological properties of 1-methoxy-canthin-6-one and to investigate on chemical requirements responsible for its biological activity, a series of novel 1,4-disubstituted and 1,4,9-trisubstituted β-carbolines and tetracyclic derivatives were designed and synthesized. In vitro cytotoxic activities of these compounds were studied in a human tumor cell line panel. Almost all compounds demonstrated antiproliferative effects, in particular against prostate cancer cells PC-3, with an IC50 values ranging between 60 and 8 μM. The most active derivatives were tested to evaluate the possible interaction with DNA and inhibition of topoisomerase I. None of these compounds were observed to stabilize the DNA–Topo I complex, thereby poisoning the reaction. In particular, 3-benzyl-1-methoxy-canthin-6-onium bromide exhibited strong inhibition of Topo I, with IC50 of 17.77 μM." @default.
- W187443672 created "2016-06-24" @default.
- W187443672 creator A5006750064 @default.
- W187443672 creator A5013736647 @default.
- W187443672 creator A5052989493 @default.
- W187443672 creator A5055282178 @default.
- W187443672 creator A5057763556 @default.
- W187443672 creator A5066659467 @default.
- W187443672 creator A5086232250 @default.
- W187443672 date "2012-01-01" @default.
- W187443672 modified "2023-10-05" @default.
- W187443672 title "1-Methoxy-Canthin-6-One and Related β-Carbolines: From Natural Compound to Synthesis and Biological Activities" @default.
- W187443672 cites W1965525286 @default.
- W187443672 cites W1966709509 @default.
- W187443672 cites W1968766701 @default.
- W187443672 cites W1970822512 @default.
- W187443672 cites W1971307855 @default.
- W187443672 cites W1975666547 @default.
- W187443672 cites W1977454516 @default.
- W187443672 cites W1985376770 @default.
- W187443672 cites W1986701803 @default.
- W187443672 cites W1989974204 @default.
- W187443672 cites W1992569136 @default.
- W187443672 cites W1994563955 @default.
- W187443672 cites W2005376465 @default.
- W187443672 cites W2008583150 @default.
- W187443672 cites W2014409042 @default.
- W187443672 cites W2022372126 @default.
- W187443672 cites W2028957763 @default.
- W187443672 cites W2036834042 @default.
- W187443672 cites W2045360350 @default.
- W187443672 cites W2068558725 @default.
- W187443672 cites W2082896443 @default.
- W187443672 cites W2088844005 @default.
- W187443672 cites W2089092225 @default.
- W187443672 cites W2096931514 @default.
- W187443672 cites W2104714902 @default.
- W187443672 cites W2106821177 @default.
- W187443672 cites W2114876761 @default.
- W187443672 cites W2136183259 @default.
- W187443672 cites W2139848279 @default.
- W187443672 cites W2147910376 @default.
- W187443672 cites W2159527710 @default.
- W187443672 cites W2163456506 @default.
- W187443672 cites W2331802721 @default.
- W187443672 cites W2589975715 @default.
- W187443672 cites W4206416471 @default.
- W187443672 cites W4244646831 @default.
- W187443672 cites W4246996250 @default.
- W187443672 doi "https://doi.org/10.1016/b978-0-444-59530-0.00004-6" @default.
- W187443672 hasPublicationYear "2012" @default.
- W187443672 type Work @default.
- W187443672 sameAs 187443672 @default.
- W187443672 citedByCount "3" @default.
- W187443672 countsByYear W1874436722017 @default.
- W187443672 countsByYear W1874436722022 @default.
- W187443672 crossrefType "book-chapter" @default.
- W187443672 hasAuthorship W187443672A5006750064 @default.
- W187443672 hasAuthorship W187443672A5013736647 @default.
- W187443672 hasAuthorship W187443672A5052989493 @default.
- W187443672 hasAuthorship W187443672A5055282178 @default.
- W187443672 hasAuthorship W187443672A5057763556 @default.
- W187443672 hasAuthorship W187443672A5066659467 @default.
- W187443672 hasAuthorship W187443672A5086232250 @default.
- W187443672 hasConcept C116073593 @default.
- W187443672 hasConcept C1491633281 @default.
- W187443672 hasConcept C179464577 @default.
- W187443672 hasConcept C185592680 @default.
- W187443672 hasConcept C190283241 @default.
- W187443672 hasConcept C202751555 @default.
- W187443672 hasConcept C203014093 @default.
- W187443672 hasConcept C2776090121 @default.
- W187443672 hasConcept C2777366897 @default.
- W187443672 hasConcept C2777832614 @default.
- W187443672 hasConcept C54355233 @default.
- W187443672 hasConcept C55493867 @default.
- W187443672 hasConcept C59822182 @default.
- W187443672 hasConcept C81885089 @default.
- W187443672 hasConcept C86803240 @default.
- W187443672 hasConcept C8891405 @default.
- W187443672 hasConcept C98274493 @default.
- W187443672 hasConceptScore W187443672C116073593 @default.
- W187443672 hasConceptScore W187443672C1491633281 @default.
- W187443672 hasConceptScore W187443672C179464577 @default.
- W187443672 hasConceptScore W187443672C185592680 @default.
- W187443672 hasConceptScore W187443672C190283241 @default.
- W187443672 hasConceptScore W187443672C202751555 @default.
- W187443672 hasConceptScore W187443672C203014093 @default.
- W187443672 hasConceptScore W187443672C2776090121 @default.
- W187443672 hasConceptScore W187443672C2777366897 @default.
- W187443672 hasConceptScore W187443672C2777832614 @default.
- W187443672 hasConceptScore W187443672C54355233 @default.
- W187443672 hasConceptScore W187443672C55493867 @default.
- W187443672 hasConceptScore W187443672C59822182 @default.
- W187443672 hasConceptScore W187443672C81885089 @default.
- W187443672 hasConceptScore W187443672C86803240 @default.
- W187443672 hasConceptScore W187443672C8891405 @default.
- W187443672 hasConceptScore W187443672C98274493 @default.