Pyrido-CARBAZOLES originally discovered in the bark of OCHROSIA ELLIPTICA. They inhibit DNA and RNA synthesis and have immunosuppressive properties.

Transfection of 9-hydroxyellipticine-resistant Chinese hamster fibroblasts with human topoisomerase IIalpha cDNA: selective restoration of the sensitivity to DNA religation inhibitors. (1/121)

In the Chinese hamster lung cell line DC-3F/9-OH-E, selected for resistance to 9-OH-ellipticine and cross-resistant to other topoisomerase II inhibitors, the amount of topoisomerase IIalpha is 4-5-fold lower than in the parental DC-3F cells, whereas topoisomerase IIbeta is undetectable. Cloning and sequencing of topoisomerase IIalpha cDNAs from DC-3F and DC-3F/9-OH-E cells revealed an allele polymorphism, one allele differing from the other by the presence of seven silent mutations and three mutations in the noncoding region. In addition, the mutated allele contains three missense mutations located close to the ATP binding site (Thr371Ser) or to the catalytic site (Ala751Gly; Ile863Thr). To analyze the contribution of these topoisomerase IIalpha alterations to their resistance phenotype, DC-3F/9-OH-E cells were transfected with an eukaryotic expression vector containing the human topoisomerase IIalpha cDNA. In one transfected clone, the amount of topoisomerase IIalpha isoform and the catalytic activity were similar to that in the parental DC-3F cells. These cells, which contain only topoisomerase IIalpha, are then a unique mammalian cell line to analyze the physiological and pharmacological properties of this enzyme. However, the restoration of a nearly normal topoisomerase IIalpha activity in the DC-3F/9-OH-E cells did not have the same effect on their sensitivity to different enzyme inhibitors; a 75% reversion of the resistance, associated with a 2-3-fold increased stabilization of the cleavable complex, was observed with both etoposide and m-AMSA, two drugs that inhibit the DNA religation step in the enzyme catalytic cycle; in contrast, the transfected cells remained fully resistant to ellipticine derivatives that did not induce the stabilization of the cleavable complex. We hypothesized that a trans-acting factor, inhibiting the induction of cleavable complex formation by drugs that are not religation inhibitors, might be present in the resistant cells. However, such a factor was not detected in in vitro experiments, and other hypotheses are discussed.  (+info)

Histology and sensitivity to anticancer drugs of two human non-small cell lung carcinomas implanted in the pleural cavity of nude mice. (2/121)

We have established two metastatic models of human non-small cell lung carcinoma (NSCLC)-the NCI-H460 large-cell carcinoma and the A549 adenocarcinoma-by inoculating tumor cells into the pleural space of nude mice. The objectives of this work were as follows: (a) to study the histological characteristics and growth and dissemination patterns of these tumors in nude mice; (b) to assess their sensitivity to drugs that have demonstrated significant clinical therapeutic effect in the treatment of NSCLC; and (c) to investigate the antitumor activity of S 16020-2, a new olivacine derivative, currently in Phase II clinical evaluation. In each of the two models, all animals developed lung tumors, resulting in 100% mortality. Histopathological study showed that these two tumors spread locally to contiguous structures, including the mediastinal pleura and diaphragm, with histological characteristics consistent with the human pathology. Anticancer drugs used for the treatment of NSCLC, such as cisplatin, doxorubicin, vinblastine, and etoposide, enhanced the life span of treated mice in the two models and were more active in the NCI-H460 than in the A549 model. The increases of survival time as compared to control groups were from 60 (P < or = 0.05) to 83% (P < or = 0.01) and from 21 to 40% for NCI-H460 and A549, respectively. Vinorelbine, paclitaxel, and irinotecan showed similar activities in the two models and increased the survival of treated mice by between 38 and 79% (P < or = 0.001) and between 58 (P < or = 0.01) and 78% in the NCI-H460 and A549 models, respectively. However, none of these drugs was curative, reflecting the resistance of this disease to chemotherapy. S 16020-2 exhibited a remarkable antitumor activity, increasing the survival by 82% (P < or = 0.01) for NCI-H460 and by 126% (P < or = 0.001) for A549. This drug was among the most active compounds in these models, thereby indicating its potential for the chemotherapy of this disease.  (+info)

In vitro and in vivo pharmacological characterizations of the antitumor properties of two new olivacine derivatives, S16020-2 and S30972-1. (3/121)

S16020-2, a new olivacine derivative and a topoisomerase II inhibitor, has recently entered clinical trials. New analogues and derivatives have been synthesized from the S16020-2 compound. Preliminary data indicate that S30972-1, one of these S16020-2 derivatives, may exhibit a comparatively higher level of antitumor potency associated with an improved therapeutic index than does S16020-2. The antitumor activities of S16020-2 and S30972-1 were therefore characterized both in vitro and in vivo, with Adriamycin and etoposide chosen as reference compounds. The in vitro data show that S30972-1 is a topoisomerase II inhibitor, mediating its activity through an ATP-dependent mechanism such as S16020-2. The two olivacine derivatives exhibited similar activities in vitro at the levels of the global growth of six human cancer cell lines, of the induction of apoptosis, and of the G2 cell cycle phase arrest. The in vivo antitumor activity characterization included the use of two murine leukemia types (P388-LEU and L1210-LEU), two murine lymphoma-like models (P388-LYM and L1210-LYM), two mammary adenocarcinomas (MXT-HI and MXT-HS), and one melanoma (B16). The data show that S30972-1 is actually more efficient in vivo than S16020-2, a feature that may relate to the fact that S30972-1 is less toxic than S16020-2. The S30972-1 compound exhibited in vivo a level of antitumor activity that was also actually higher than that exhibited by Adriamycin and similar to that exhibited by etoposide.  (+info)

Cellular resistance to the antitumor DNA topoisomerase II inhibitor S16020-2: importance of the N-[2(Dimethylamino)ethyl]carbamoyl side chain. (4/121)

The new olivacine derivative S16020-2 (NSC-659687) is a DNA topoisomerase II inhibitor endowed with a remarkable antitumor activity against various experimental tumors. In vitro physicochemical properties of this compound, in particular its interaction with DNA and DNA topoisomerase II, were very similar to those of ellipticine derivatives, except for a strictly ATP-dependent mechanism of cleavable complex induction. From the Chinese hamster lung fibroblast cell line DC-3F, a subline resistant to S16020-2, named DC-3F/S16, was selected by adding stepwise increasing concentrations of the drug to the cell growth medium. Whereas DC-3F/9-OH-E cells, a DC-3F subline resistant to 9-hydroxy-ellipticine, are cross-resistant to S16020-2, DC-3F/S16 cells are only very weakly cross-resistant to ellipticine derivatives, indicating that, despite their structural similarity, these compounds may differ in their mechanisms of action. Uptake and efflux rates of S16020-2 were identical in the resistant and the sensitive cells. Topoisomerase IIalpha was expressed at the same level in both sensitive and resistant cells, whereas expression of the beta-enzyme was approximately 50% lower in the resistant cells. Sequencing of both alpha- and beta-isoform cDNAs revealed a point mutation that converts Arg(486) to a Gly in the alpha cDNA, whereas the beta cDNA was not modified. This amino acid substitution in a highly conserved sequence of the enzyme appears to be responsible for the resistance to S16020-2. Comparative analysis of the properties of the ellipticine and S16020-2-resistant cells suggests that S16020-2, which is a DNA intercalator, might also interact with this enzyme amino acid sequence through its side chain.  (+info)

Astaxanthin accumulation in Haematococcus requires a cytochrome P450 hydroxylase and an active synthesis of fatty acids. (5/121)

Astaxanthin accumulation by green microalgae is a natural phenomenon known as red snows and blood rains. The fact that astaxanthin synthesis requires oxygen, NADPH and Fe(2+) led Cunningham and Gantt [Annu. Rev. Plant Physiol. Plant Mol. Biol. 49 (1998) 557-583] to propose that a cytochrome P450-dependent enzyme might be involved in the transformation of beta-carotene to astaxanthin. In Haematococcus only esterified astaxanthin molecules accumulate, but it is not determined whether a fatty acid synthesis should occur simultaneously to allow pigment accumulation. The aim of this contribution was to answer these two questions using specific inhibitors of beta-carotene (norflurazon) and fatty acid (cerulenin) synthesis, and of cytochrome P450 enzyme activity (ellipticine).  (+info)

The olivacine S16020 enhances the antitumor effect of ionizing radiation without increasing radio-induced mucositis. (6/121)

The combination of a novel topoisomerase II inhibitor, S16020, and ionizing radiation (IR) was investigated with the aim of assessing normal tissue tolerance using a mouse mucosal lip model and antitumor activity in a human carcinoma (HEP2) cell line. No increase of acute mucosal reactions was seen when combining S16020 with IR as compared with IR alone. Using clonogenic cell survival assay, a marked enhancement of HEP2 cell killing was found when S16020 was combined with irradiation. Additional in vivo combination of S16020-IR was able to increase markedly the antitumor efficacy as compared with S16020 or irradiation alone. Interestingly, the radiosensitization effect in vivo was observed at relatively low and nontoxic concentrations of S16020, and no dose-effect relationship was found beyond 30 mg/kg. In conclusion, the combination of IR and S16020 seems promising to enhance antitumor activity without increasing deleterious effect in normal tissues and to provide the basis for a new radio-chemotherapy combination.  (+info)

Viral and immunologic follow up of 4 to 9 years of AIDS treatments by quadruple combinations of virostatics including integrase inhibitors applied in short sequences differing by drug rotation. (7/121)

AIM: To present the 4 to 9 years (median: 6 years) treatment follow up of 10 HIV1-AIDS patients, 9 at AIDS and 1 at A3 stages. METHODS: We have applied from 1992 to 1994, AZT combined with 2 integrase inhibitors, acriflavine and hydroxy-methyl-ellipticine. We could shift, in 1994, to combinations of 3 drugs including two more retrotranscriptase inhibitors (RTI), ddI and ddC, and, after 1995, to combinations of 4 drugs including also two other RTI, d4T and 3TC, and 3 protease inhibitors (PI), indinavir, ritonavir, and saquinavir. In 1998, as cobalamine was shown by an in vitro test, to act as integrase inhibitor, vitamin B12 was added in cycles of various lengths. Every three weeks, not only the investigations were repeated, but the virostatics were changed. RESULTS: No grade 2 virostatics toxicity has been registered. The viral loads (VL) decreased according to exponential curves. Their initial parts obeyed first order kinetics. The second parts were and still are asymptotic. The first parts could be rectilinear or sinuous. The sinuosities were associated to cofactors present before treatment (chimerism, UV irradiation, hepatitis C or B and C, brain toxoplasmosis). The asymptotic parts, whose VL were below PCR detectable levels, presented discrete, reversible HIV1 rebounds, associated to other cofactors (such as herpes zoster, herpes 6, CMV, flat condyloma, and influenza). Among immunologic parameters, the monocyte and CTL numbers increased and presented, during the rapidly decreasing part of VL curve, a significant inverse correlation with it. Neither CD4+ nor suppressor T-cell (STC) numbers presented such correlation. Near 100 % of CTL were CD28+. Later, vitamin B12 applications increased monocyte and CD28+ CTL numbers, and appeared to reinforce VL stabilization. CONCLUSION: The combinations of inhibitors affecting 3 retrovirus targets, retrotranscriptase, integrase, and protease have given to 10 out of 10 AIDS patients survivals varying today between 4 to 9 years, in excellent conditions. The UVA-pretreated patient is the only one presenting a not maximally reduced asymptotic VL, while his CD4+ and STC have been absent for 8 years. Other patient VL regressed exponentially to become asymptotic, below PCR detectable levels.  (+info)

Cardioprotective effects of 9-hydroxyellipticine on ischemia and reperfusion in isolated rat heart. (8/121)

We determined the effect of 9-hydroxyellipticine (9HE) on ryanodine receptor (RyR) and cardiac function after global ischemia in isolated rat hearts. The binding of [3H]-ryanodine in rabbit cardiac sarcoplasmic reticulum was displaced by 9HE in a biphasic manner corresponding to the two sites model with IC50 values of 6.1 microM and 55 mM. The increase of the intracellular Ca2+ concentration induced by caffeine in CHO cells expressing cardiac-type RyR was suppressed by 9HE in a concentration-dependent manner. Pretreatment of the heart with 9HE decreased the total duration of reperfusion-induced ventricular fibrillation (VF) and delayed the onset of VF. There was also a significant recovery of contractile force of ischemic hearts following 9HE. Unlike nifedipine, an L-type Ca2+-channel blocker, 9HE did not suppress the contraction of rat papillary muscles. Thus, 9HE exerts the cardioprotective effects against ischemia /reperfusion injury without changing hemodynamic indices.  (+info)

Ellipticines are a class of naturally occurring alkaloids that have been isolated from various plants, including those in the family Apocynaceae. These compounds have been found to exhibit various biological activities, including anti-cancer and anti-microbial properties.

Ellipticines have a unique chemical structure, characterized by a planar, aromatic core with two side chains that contain nitrogen atoms. This structure allows ellipticines to intercalate into DNA, disrupting its normal function and leading to cell death. As a result, ellipticines have been studied as potential anti-cancer agents, particularly for the treatment of drug-resistant cancers.

In addition to their anti-cancer properties, ellipticines have also been found to exhibit antibacterial, antifungal, and antiparasitic activities. However, further research is needed to fully understand the mechanisms behind these effects and to determine the safety and efficacy of ellipticines as therapeutic agents.

... and toxicity of ellipticines, ellipticinium, and 9-hydroxy derivatives: preliminary clinical trials of 2-methyl-9-hydroxy ...
... ellipticines MeSH D03.438.473.402.681.444 - ibogaine MeSH D03.438.473.402.681.722 - strychnine MeSH D03.438.473.402.681.827 - ... ellipticines MeSH D03.132.436.681.444 - ibogaine MeSH D03.132.436.681.722 - strychnine MeSH D03.132.436.681.827 - vinca ... ellipticines MeSH D03.494.148.500 - ondansetron MeSH D03.494.148.750 - staurosporine MeSH D03.494.154.333 - harmaline MeSH ...
... and toxicity of ellipticines, ellipticinium, and 9-hydroxy derivatives: preliminary clinical trials of 2-methyl-9-hydroxy ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Compounds formed by condensation of secologanin with tryptamine resulting in a tetrahydro-beta-carboline which is processed further to a number of bioactive compounds. These are especially found in plants of the APOCYNACEAE; LOGANIACEAE; and RUBIACEAE families ...
Of which amitriptyline hcl used for pain ellipticines use unresolvable hanumans stripping circa yourselves plastic wormholes? ...
Ellipticines:metabolism, Humans, Liposomes, Microsomes,. Citation ...
Ellipticines D3.438.473.144.249 D3.633.100.473.144.249 D3.438.473.402.681.333 D3.633.100.473.402.681.333 D3.494.148.249 D3.633. ...
We identified a group of ellipticines that targets the G-quadruplexes in the PDGFR-ß promoter, and from this series of ...
Ellipticines:administration & dosage, Histone Deacetylase Inhibitors:administra. OBJECTIVES: Valproic acid (VPA) and ...
One of several indole alkaloids extracted from Tabernanthe iboga, Baill. It has a complex pharmacological profile, and interacts with multiple systems of neurotransmission. Ibogaine has psychoactive properties and appears to modulate tolerance to opiates ...
Synthesis and evaluation of novel ellipticines as potential anti-cancer agents - Deane, Fiona M., OSullivan, Elaine C., ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Title: Analysis of structural requirements for Ah receptor antagonist activity: ellipticines, flavones, and related compounds. ... MeSH Terms: Animals; DNA/metabolism; Ellipticines/pharmacology*; Enhancer Elements, Genetic; Flavonoids/pharmacology*; Male; ...
1-Functionalized 5,6-Dimethyl-6H-pyrido[4,3-b]carbazoles (Ellipticines) and Analogues: A New Rapid Synthesis. Emile Bisagni,* ...
Ellipticines Preferred Term Term UI T014075. Date01/01/1999. LexicalTag NON. ThesaurusID NLM (1975). ... Ellipticines Preferred Concept UI. M0007239. Registry Number. 0. Scope Note. Pyrido-CARBAZOLES originally discovered in the ... Ellipticines. Tree Number(s). D03.132.436.681.333. D03.633.100.473.144.249. D03.633.100.473.402.681.333. D03.633.100.496. ...
Ellipticines Preferred Term Term UI T014075. Date01/01/1999. LexicalTag NON. ThesaurusID NLM (1975). ... Ellipticines Preferred Concept UI. M0007239. Registry Number. 0. Scope Note. Pyrido-CARBAZOLES originally discovered in the ... Ellipticines. Tree Number(s). D03.132.436.681.333. D03.633.100.473.144.249. D03.633.100.473.402.681.333. D03.633.100.496. ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Ellipticines D3.438.473.144.249. Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500. Embolism, Paradoxical ...
Radioactive N0000010109 eletriptan N0000167033 Ellagic Acid N0000167257 Ellipticines N0000178587 Elongation Factor 2 Kinase ...
... ellipticines, mitoxantrone and epipodophyllotoxins. Results from the T4 model system provided a convincing demonstration that ...
Ellipticines:pharmacokinetics, Humans, Microsomes, Liver:drug effects, Oxidation-Reduction:drug effects, Peroxidases: ...
F4.669.224.300 Ellipticines D3.438.473.144.249 Embolism, Cholesterol C14.907.355.350.404 C14.907.355.350.454.500 Embolism, ...
OSullivan E, Miller C, Deane F and McCarthy F (2013) Emerging Targets in the Bioactivity of Ellipticines and Derivatives , ...
Ellipticines:chemistry, Enzyme Activation:drug effects, Enzyme Inhibitors:chemistry, Horseradish Peroxidase:antagonists & ...
Compounds formed by condensation of secologanin with tryptamine resulting in a tetrahydro-beta-carboline which is processed further to a number of bioactive compounds. These are especially found in plants of the APOCYNACEAE; LOGANIACEAE; and RUBIACEAE families ...
  • Analysis of structural requirements for Ah receptor antagonist activity: ellipticines, flavones, and related compounds. (nih.gov)