Toxicological and pharmacological studies on 9-hydroxy-ellipticine in mice

Cros, S.; Sorbara, R; Moisand, Christiane; Dat-Xuong, N; Lecointe, P.; Paoletti, Claude

doi:10.1016/0041-008x(75)90074-5

Cited by 18 publications

(5 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatment with olivacine alone caused leucopenia, mainly in terms of lymphocy-topenia and neutropenia. Similar results for a decrease in white blood cells have been described (Cros et al, 1975) for treated mice infected by Llzl0 leukaemia with another pyridocarbazole alkaloid, 9-hydroxielllipticine: a reduction in polynuclear neutrophils was observed after 19 injections, when the drug was administered once every 3 days. Leucopenia was also observed in dogs (Pham-Huu-Chanh et al, 1974) when doses of 5 to 10 mg/kg ellipticine were applied over a period of 2 to 5 weeks.…”

Section: Discussionsupporting

confidence: 82%

Olivacine plus coadjuvants in the treatment of murine leukaemia

Oliveira

Filho

1994

Phytotherapy Research

View full text Add to dashboard Cite

Administration of olivacine, l,S-dimethyl-6H-pyrido[4,3-b] carbazole to mice inoculated with 1 6 , lo' and 102 leukaemic cells (L,,,,) produced significant survival in all treated groups which was not altered by association with the naturally occurring nucleoside deoxycytidine. Treatment with olivacine plus heterologous serum caused leucocytosis due to neutrophilia, lymphocytosis and monocytosis, as opposed to treatment with olivacine alone, which produced leucopenia due to neutropenia and lymphocytopenia. MATERIAL AND METHODSOlivacine. This was obtained from the root bark of Aspidosperma nigricans or Aspidosperma olivaceum, extracted with ethanol and purified in the usual way for pyridocarbazole alkaloids (Gilbert, 1965). Deoxycytidine.A dose of 50 mg/kg of 2-deoxycytidinium chloride (Merck, Darmstadt, FRG) was injected intraperitoneally on a daily regimen.Coadjuvant. Heterologous hyperimmune serum (horse), supplied by Dr P. Bueno (Instituto Biologico, Sao Paulo), was used; 0.2 mL ampules were applied subcutaneously at 5-day intervals.

show abstract

Section: Discussionsupporting

confidence: 82%

Olivacine plus coadjuvants in the treatment of murine leukaemia

Oliveira

Filho

1994

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…The indeno [1,2-b]quinoxaline nucleus of IQ-1S is a flat aromatic ring structure (Ghalib et al, 2010), and planar fused heterocyclic compounds can exhibit a wide variety of pharmacological activities, including DNA intercalation and inhibition of topoisomerases I/II (Deady et al, 1997;Moorthy et al, 2013). Although we did not evaluate potential DNAintercalating and topoisomerase-inhibiting properties of IQ-1S, this compound was noncytotoxic at high concentrations (Schepetkin et al, 2012), whereas many DNA intercalators (e.g., ellipticine) and topoisomerase inhibitors are cytotoxic (Cros et al, 1975). On the other hand, further development of ellipticine analogs led to the synthesis of DNA-intercalating agents with antiviral, cytotoxic, and immunomodulatory properties, including compound B220 [2,3-dimethyl-6(2-dimethylaminoethyl)-6H-indolo-(2,3-b)quinoxaline] and Rabeximod (Harbecke et al, 1999;Hultqvist et al, 2009).…”

Section: Foxp3mentioning

confidence: 99%

Anti-Inflammatory Effects and Joint Protection in Collagen-Induced Arthritis after Treatment with IQ-1S, a Selective c-Jun N-Terminal Kinase Inhibitor

Schepetkin

Kirpotina

Hammaker

et al. 2015

J Pharmacol Exp Ther

View full text Add to dashboard Cite

c-Jun N-terminal kinases (JNKs) participate in many physiologic and pathologic processes, including inflammatory diseases. We recently synthesized the sodium salt of IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime) and demonstrated that it is a high-affinity JNK inhibitor and inhibits murine delayed-type hypersensitivity. Here we show that IQ-1S is highly specific for JNK and that its neutral form is the most abundant species at physiologic pH. Molecular docking of the IQ-1S syn isomer into the JNK1 binding site gave the best pose, which corresponded to the position of cocrystallized JNK inhibitor SP600125 (1,9-pyrazoloanthrone). Evaluation of the therapeutic potential of IQ-1S showed that it inhibited matrix metalloproteinase 1 and 3 gene expression induced by interleukin-1b in human fibroblast-like synoviocytes and significantly attenuated development of murine collagen-induced arthritis (CIA). Treatment with IQ-1S either before or after induction of CIA resulted in decreased clinical scores, and joint sections from IQ-1S-treated CIA mice exhibited only mild signs of inflammation and minimal cartilage loss compared with those from control mice. Collagen II-specific antibody responses were also reduced by IQ-1S treatment. By contrast, the inactive ketone derivative 11H-indeno[1,2-b]quinoxalin-11-one had no effect on CIA clinical scores or collagen II-specific antibody titers. IQ-1S treatment also suppressed proinflammatory cytokine and chemokine levels in joints and lymph node cells. Finally, treatment with IQ-1S increased the number of Foxp3 CD251 regulatory T cells in lymph nodes. Thus, IQ-1S can reduce inflammation and cartilage loss associated with CIA and can serve as a small-molecule modulator for mechanistic studies of JNK function in rheumatoid arthritis.

show abstract

“…[45][46] The major shortcomings in the usage of neutral ellipticine as a pharmaceutical are its toxicity and low solubility in water, but the cationic species, ellipticinium, is more soluble in water than neutral ellipticine. 47 At a pH value below 7.4, due to protonation of pyridine-like nitrogen, cationic species are formed. 48 We can overcome the problem of low solubility in an aqueous media by attaching the drug to a polymer, peptide or micelle.…”

Section: Introductionmentioning

confidence: 99%

Photophysical and photodynamical study of ellipticine: an anticancer drug molecule in bile salt modulated in vitro created liposome

Thakur

Das

Chakraborty

2012

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

The entrapment of anticancer drug ellipticine in the dipalmitoylphosphocholine (DPPC) liposome and its release by addition of three different bile salts, namely sodium deoxycholate, cholate and taurocholate, have been studied by steady state and time resolved fluorescence spectroscopy. We found that the release of the drug from a liposome depends on the degree of penetration of bile salts. Among the three bile salts, deoxycholate was most effective in releasing the drug from the hydrocarbon core of the liposome because of its high insertion ability owing to its maximum hydrophobicity. The time resolved studies revealed that with addition of bile salt to the liposome solution, ellipticine molecules were removed from the hydrocarbon core and were entrapped in an interfacial region of liposomes by electrostatic interaction. This led to an increase in the shorter lifetime component. On the other hand, the longer lifetime component decreased because bile salts wet the hydrocarbon core of the liposome by carrying hydrogen bonded water. Entrapment of ellipticine in the interfacial region was also supported by an increase in the rotational relaxation time with addition of bile salt.

show abstract

Toxicological and pharmacological studies on 9-hydroxy-ellipticine in mice

Cited by 18 publications

References 7 publications

Olivacine plus coadjuvants in the treatment of murine leukaemia

Olivacine plus coadjuvants in the treatment of murine leukaemia

Anti-Inflammatory Effects and Joint Protection in Collagen-Induced Arthritis after Treatment with IQ-1S, a Selective c-Jun N-Terminal Kinase Inhibitor

Photophysical and photodynamical study of ellipticine: an anticancer drug molecule in bile salt modulated in vitro created liposome

Contact Info

Product

Resources

About