当前位置： SCI文献检索 > BIOCHEMICAL PHARMACOLOGY期刊下所有文献 > Mechanism of action of a novel "combi-triazene" engineered to possess a polar functional group on the alkylating moiety: evidence for enhancement of potency.

Mechanism of action of a novel "combi-triazene" engineered to possess a polar functional group on the alkylating moiety: evidence for enhancement of potency.

Abstract：

:Previous studies showed that SMA41, a 3-methyltriazene termed "combi-molecules" possessing a dual epidermal growth factor receptor (EGFR)/DNA targeting properties induced potent antiproliferative activity against alkylating-agent-resistant cells expressing EGFR in vitro. However, despite its marked potency, its antitumour activity in vivo was significantly hampered by its poor hydrosolubility and the moderate reactivity of its alkylating moiety. To circumvent this problem, we designed the quinazolinotriazene ZRBA1 to contain a N,N-dimethylaminoethyl group grafted to the 3-position of the triazene chain where it could serve both as a water soluble and a more potent alkylating moiety. ZRBA1 exhibited five-fold stronger EGFR tyrosine kinase (TK) inhibitory activity (IC(50)=37nM) than SMA41, decomposed into a 6-amino-quinazoline FD105 (IC(50)=200nM) and preferentially blocked EGF- over platelet-derived growth factor (PDGF)-or serum-induced cell growth. ZRBA1 induced DNA damage, concomitantly blocked EGF-stimulated EGFR phosphorylation by a partially irreversible mechanism in MDA-MB-468 breast cancer cells, and induced partially irreversible antiproliferative activity. It also prevented EGFR-mediated MAP kinase activation and, in contrast to FD105 and SMA41, induced high levels of apoptosis. Furthermore, ZRBA1 showed significantly greater antitumor activity (p<0.05) than SMA41 in the human MDA-MB-468 breast cancer xenograft model. The results in toto indicate that the appendage of N,N-dimethylaminoethyl to combi-triazenes may be an alternative to the reduced hydrosolubility and also to the lack of potency of monofunctional combi-triazenes against resistant tumours.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Brahimi F,Rachid Z,McNamee JP,Alaoui-Jamali MA,Tari AM,Jean-Claude BJ

doi

10.1016/j.bcp.2005.04.037

subject

Has Abstract

pub_date

2005-08-15 00:00:00

pages

511-9

issue

4

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(05)00230-3

journal_volume

70

pub_type

杂志文章

相关文献

BIOCHEMICAL PHARMACOLOGY文献大全
  • Resistance of HepG2 cells against the adverse effects of ethanol related to neutral lipid and phospholipid metabolism.

    abstract：:The influence of both short- and long-term ethanol exposure on the lipid metabolism was determined in the human hepatoma cell line HepG2. Ethanol did not cause any cytotoxicity or lipid peroxidation even after 7 days of 100 mM ethanol treatment of HepG2 cells. Incubation of cells in the presence of [1-(14)C]ethanol de...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(02)00896-1

    authors： Jiménez-López JM,Carrasco MP,Segovia JL,Marco C

    更新日期：2002-04-15 00:00:00

  • Effects of nitric oxide and hydrogen peroxide on histamine release from RBL-2H3 cells.

    abstract：:We have studied the effect of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)), two reactive oxygen species (ROS) on histamine release (HR) from RBL-2H3 cells, a rat mucosal-type mast cell line. Marked HR was elicited by antigen (DNP-HSA), calcium ionophore A23187, sodium fluoride or phospholipase C, but not with co...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(01)00770-5

    authors： Wan BY,Peh KH,Ho M,Assem ES

    更新日期：2001-12-01 00:00:00

  • Halogenated pyrrolopyrimidine analogues of adenosine from marine organisms: pharmacological activities and potent inhibition of adenosine kinase.

    abstract：:Two novel halogenated pyrrolopyrimidine analogues of adenosine, isolated from marine sources, have been examined for pharmacological and biochemical activities. 4-Amino-5-bromo-pyrrolo[2,3-d]pyrimidine, from a sponge of the genus Echinodictyum, had bronchodilator activity at least as potent as theophylline but with a ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(84)90225-9

    authors： Davies LP,Jamieson DD,Baird-Lambert JA,Kazlauskas R

    更新日期：1984-02-01 00:00:00

  • Changes in the biliary excretion of organic anions following exhaustive exercise in rats.

    abstract：:The effect of exhaustive exercise on the hepatobiliary transport of organic anions was investigated in rats. Animals were run on a rodent treadmill at 24 m/min up a 12% grade (152 +/- 15 min). Exercise resulted in significant hypoglycaemia (-46%) and increased plasma levels of lactate (+12%), together with a marked re...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(90)90094-2

    authors： Villa JG,Collado PS,Almar MM,Gonzalez J

    更新日期：1990-12-01 00:00:00

  • Potentiation by febrifugine of host defense in mice against Plasmodium berghei NK65.

    abstract：:The effect of febrifugine, the main alkaloidal constituent of an antimalarial crude drug, Dichroa febrifuga Lour., on protective immunity in mice infected with erythrocytic stage Plasmodium berghei NK65 was investigated. Febrifugine was administered orally, at a dose of 1 mg/kg/day, to mice before and/or after they we...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(99)00244-0

    authors： Murata K,Takano F,Fushiya S,Oshima Y

    更新日期：1999-11-15 00:00:00

  • Developmental correlation of higher levels of estrogen binding by macromolecules in rat liver supernatant and of increases in plasma renin substrate levels after estrogen administration.

    abstract：:Developmental correlation of higher levels of estrogen binding by macromolecules in rat liver supernatant and of increases in plasma renin substrate levels after estrogen administration is reported. Gel filtration columns were used to separate bound from free radioactivity in studying binding of radioactive estradiol...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(77)90467-1

    authors： Eisenfeld AJ,Krakoff LR,Aten RF

    更新日期：1977-05-15 00:00:00

  • The signalling axis mediating neuronal apoptosis in response to [Pt(O,O'-acac)(γ-acac)(DMS)].

    abstract：:It was previously shown that [Pt(O,O'-acac)(γ-acac)(DMS)] induces apoptosis in various cancer cells and exerts antimetastatic responses in vitro. In rats, [Pt(O,O'-acac)(γ-acac)(DMS)] reaches the central nervous system in quantities higher than cisplatin causing less excitotoxicity. The aim of the present paper was to...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2011.03.007

    authors： Muscella A,Calabriso N,Vetrugno C,Fanizzi FP,De Pascali SA,Marsigliante S

    更新日期：2011-06-01 00:00:00

  • Current perspectives on parathyroid hormone (PTH) and PTH-related protein (PTHrP) as bone anabolic therapies.

    abstract：:Osteoporosis is characterized by low bone mineral density and/or poor bone microarchitecture leading to an increased risk of fractures. The skeletal alterations in osteoporosis are a consequence of a relative deficit of bone formation compared to bone resorption. Osteoporosis therapies have mostly relied on antiresorp...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.bcp.2013.03.002

    authors： Esbrit P,Alcaraz MJ

    更新日期：2013-05-15 00:00:00

  • alpha-fluoro-beta-alanine: effects on the antitumor activity and toxicity of 5-fluorouracil.

    abstract：:We have shown previously that (R)-5-fluoro-5,6-dihydrouracil (FUraH(2)) attenuates the antitumor activity of 5-fluorouracil (FUra) in rats bearing advanced colorectal carcinoma. Presently, we found that alpha-fluoro-beta-alanine (FBAL), the predominant catabolite of FUra that is formed rapidly via FUraH(2), also decre...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(99)00408-6

    authors： Cao S,Baccanari DP,Rustum YM,Davis ST,Tansik RL,Porter DJ,Spector T

    更新日期：2000-04-15 00:00:00

  • Bioactivation of N-arylhydroxamic acids by rat hepatic N-acetyltransferase. Detection of multiple enzyme forms by mechanism-based inactivation.

    abstract：:Enzymatic N,O-acyltransfer of carcinogenic N-arylhydroxamic acids such as N-hydroxy-2-acetylaminofluorene (N-OH-AAF) results in the production of reactive electrophiles that can bond covalently with nucleophiles and also can cause inactivation of acyltransferase activity in a mechanism-based manner. Incubation of part...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(90)90277-r

    authors： Wick MJ,Hanna PE

    更新日期：1990-03-15 00:00:00

  • Changes in methionine metabolism induced by D-galactosamine in isolated rat hepatocytes.

    abstract：:We studied several steps of methionine metabolism in isolated rat hepatocytes both with and without the presence of a hepatotoxic agent (D-galactosamine). By use of selective labelling either on methyl or on carboxyl groups, we showed that intracellular methionine is used preferentially for the methylation of phosphol...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(86)90699-4

    authors： Ozturk M,Lemonnier F,Cresteil D,Lemonnier A

    更新日期：1986-12-01 00:00:00

  • Selective 3-hydroxylation deficiency of lidocaine and its metabolite in Dark Agouti rats.

    abstract：:Selective and marked 3-hydroxylase deficiency of lidocaine and its N-deethylated metabolite, MEGX, were observed in male and female DA rats. These findings suggest that cytochrome P450 isozymes metabolizing debrisoquine may be involved in the 3-hydroxylations of lidocaine and MEGX in rats and humans. ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(91)90333-z

    authors： Masubuchi Y,Umeda S,Chiba M,Fujita S,Suzuki T

    更新日期：1991-07-15 00:00:00

  • The role of intracellular calcium in A-23187 stimulated and beta-adrenoceptor blocking drug treated blood platelets.

    abstract：:A significant concentration-dependent difference was found between beta-adrenoceptor blocking drugs in their ability to inhibit A23187-induced isolated platelet aggregation. In the absence of extracellular calcium ions the following rank order of potency to inhibit calcium ionophore stimulated platelet aggregation was...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(94)90257-7

    authors： Nosál R,Jancinová V,Petríková M

    更新日期：1994-06-15 00:00:00

  • Tumor cell escape from therapy-induced senescence.

    abstract：:H460 non-small cell lung, HCT116 colon and 4T1 breast tumor cell lines induced into senescence by exposure to either etoposide or doxorubicin were able to recover proliferative capacity both in mass culture and when enriched for the senescence-like phenotype by flow cytometry (based on β-galactosidase staining and cel...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2018.12.013

    authors： Saleh T,Tyutyunyk-Massey L,Murray GF,Alotaibi MR,Kawale AS,Elsayed Z,Henderson SC,Yakovlev V,Elmore LW,Toor A,Harada H,Reed J,Landry JW,Gewirtz DA

    更新日期：2019-04-01 00:00:00

  • Covalent binding of the anticancer drug ellipticine to DNA in V79 cells transfected with human cytochrome P450 enzymes.

    abstract：:Ellipticine is a potent antineoplastic agent whose mechanism of action is considered to be based mainly on DNA intercalation and/or inhibition of topoisomerase II. Recently, we found that ellipticine also forms covalent DNA adducts and that the formation of the major adduct is dependent on the activation of ellipticin...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(02)01072-9

    authors： Frei E,Bieler CA,Arlt VM,Wiessler M,Stiborová M

    更新日期：2002-07-15 00:00:00

  • Griseofulvin: a novel interaction with bovine brain tubulin.

    abstract：:Griseofulvin is an anti-fungal drug whose mechanism of action is directed against microtubules. Although it inhibits the assembly of mammalian brain tubulin, its binding to tubulin has not been directly measured successfully. We have examined the interaction of griseofulvin with tubulin fluorometrically by measuring t...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(95)02406-9

    authors： Chaudhuri AR,Ludueña RF

    更新日期：1996-04-12 00:00:00

  • Effects of the desensitization by morphine of the opiate-dependent adenylate cyclase system in the rat striatum on the activity of the inhibitory regulatory G protein.

    abstract：:Opiates act through a specific receptor to inhibit the striatal adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4,6.1.1] and stimulate a high-affinity GTPase (EC 3.6.1). The present study analyzes the functions of the striatal adenylate cyclase complex following chronic morphine treatment in the rat. The in...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(88)90507-2

    authors： Tirone F,Viganó A,Groppetti A,Parenti M

    更新日期：1988-03-15 00:00:00

  • Phospholipase A2 activity in carrageenin-induced inflammatory tissue of rats.

    abstract：:Phospholipase A2 activity was detected in 7-day-old carrageenin-induced inflammatory tissue of rats using a synthetic substrate. 1-acyl-2-[3H]arachidonyl-phosphatidylcholine. The inflammatory tissue was homogenized in saline containing 1 M KCl, and the 105,000 g supernatant fraction was placed on a Sephadex G-100 colu...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(82)90275-1

    authors： Ohuchi K,Watanabe M,Numajiri N,Tsurufuji S

    更新日期：1982-09-15 00:00:00

  • Mixed function oxidase in the mammary gland and liver microsomes of lactating rats. Effects of 3-methylcholanthrene and beta-naphthoflavone.

    abstract：:Mammary gland and liver microsomes of lactating rats were examined for the components of mixed function oxidase and related enzyme activities. Cytochrome b5, NADH- and NADPH- dependent cytochrome c reductase activities were 15-, 6- and 10-fold lower, respectively, in the mammary gland than in the liver microsomes. The...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(82)90217-9

    authors： Ritter CL,Malejka-Giganti D

    更新日期：1982-01-15 00:00:00

  • Beneficial effects of L-carnitine in myoblastic C2C12 cells. Interaction with zidovudine.

    abstract：:L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable L-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing L-carnitine. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(03)00110-2

    authors： Georges B,Galland S,Rigault C,Le Borgne F,Demarquoy J

    更新日期：2003-05-01 00:00:00

  • Site-specific DNA cleavage by Cu(II) complexes of podophyllotoxin derivatives.

    abstract：:Site-specific DNA cleavage in the presence of Cu(II) complexes of podophyllotoxin derivatives was investigated with a modified Sanger sequencing method. Cu(II) complexes of 4'-demethylepipodophyllotoxin (DEPD) and syringic acid (SA) cleaved M13mp18 single-strand DNA site-specifically at both cytosine (C) and guanine (...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(94)90324-7

    authors： Yamashita A,Tawa R,Imakura Y,Lee KH,Sakurai H

    更新日期：1994-05-18 00:00:00

  • The inhibitory effect of HOE 731 in isolated rabbit gastric glands.

    abstract：:HOE 731, a substituted thienoimidazole derivative, was studied on [14C] aminopyrine uptake and oxygen consumption in isolated rabbit gastric glands. HOE 731 caused a concentration-dependent inhibition of [14C]aminopyrine uptake during histamine and dbcAMP stimulation. The inhibition during dbcAMP stimulation was in ac...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(90)90360-w

    authors： Herling AW,Becht M,Lang HJ,Scheunemann KH,Weidmann K,Scholl T,Rippel R

    更新日期：1990-10-15 00:00:00

  • Solubilization of active somatostatin receptors from rabbit retina.

    abstract：:Somatostatin receptors from rabbit retinal membranes were solubilized in an active form using a mixture of the detergent n-octyl b-D-glucopyranoside (OG) and CHAPS. The binding of [125I]-Try11-somatostatin to the soluble extract was saturable and of high affinity, with an apparent affinity constant (Kd) of 0.60 +/- 0....

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(93)90439-4

    authors： Liapakis G,Politou E,Thermos K

    更新日期：1993-05-05 00:00:00

  • DUP 785 (NSC 368390): schedule-dependency of growth-inhibitory and antipyrimidine effects.

    abstract：:DUP 785 (NSC 368390; Brequinar sodium) is a new inhibitor of pyrimidine de novo biosynthesis with antitumor activity against several experimental tumors. DUP 785 inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, blocking the conversion of dihydroorotate to orotate. We examined the influence of exposure t...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(88)90636-3

    authors： Schwartsmann G,Peters GJ,Laurensse E,de Waal FC,Loonen AH,Leyva A,Pinedo HM

    更新日期：1988-09-01 00:00:00

  • Elevation of rat pulmonary, hepatic and lung surfactant lipids by fly ash inhalation.

    abstract：:Fly ash contains many polycyclic aromatic hydrocarbons and genotoxic trace elements. In rats, fly ash exposure profoundly affects lung and liver histology. In the present study, the effect of fly ash inhalation on lung and liver lipids of rats was examined. Male Wistar strain rats were exposed daily to fly ash (0.27 +...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(91)90476-l

    authors： Chauhan SS,Misra UK

    更新日期：1991-01-15 00:00:00

  • Substituted flavones as aryl hydrocarbon (Ah) receptor agonists and antagonists.

    abstract：:The structure-dependent aryl hydrocarbon (Ah) receptor agonist and antagonist activities of the following substituted flavones were investigated: flavone, 4'-methoxy-, 4'-amino-, 4'-chloro-, 4'-bromo-, 4'-nitro-, 4'-chloro-3'-nitro-, 3'-amino-4'-hydroxy-, 3',4'-dichloro-, and 4'-iodoflavone. The halogenated flavones e...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(96)00063-9

    authors： Lu YF,Santostefano M,Cunningham BD,Threadgill MD,Safe S

    更新日期：1996-04-26 00:00:00

  • Cytotoxicity of BMS-181174. Effects of hypoxia, dicoumarol, and repair deficits.

    abstract：:The mitomycin C (MC) analog BMS-181174 (previously designated as BMY25067) has been shown to be active against a variety of solid tumors in mice. The activity of this compound against tumor cell lines resistant to MC and the different toxicity profiles of BMS-181174 and MC suggested that there may be significant diffe...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(95)00264-z

    authors： Rockwell S,Kemple B,Kelley M

    更新日期：1995-10-12 00:00:00

  • The inhibition of TNF-alpha-induced NF-kappaB activation by marine natural products.

    abstract：:The deregulated activation of NF-kappaB is associated with cancer development and inflammatory diseases. With an aim to find new NF-kappaB inhibitors, we purified and characterized compounds from extracts of the Fijian sponge Rhabdastrella globostellata, the crinoid Comanthus parvicirrus, the soft corals Sarcophyton s...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2009.05.009

    authors： Folmer F,Jaspars M,Solano G,Cristofanon S,Henry E,Tabudravu J,Black K,Green DH,Küpper FC,Aalbersberg W,Feussner K,Dicato M,Diederich M

    更新日期：2009-09-15 00:00:00

  • Effects of sulfobromophthalein and ethacrynic acid on glyceryl trinitrate relaxation.

    abstract：:The effects of sulfobromophthalein (SBP) and ethacrynic acid (ECA), both inhibitors of glutathione S-transferase (GST), or glyceryl trinitrate (GTN)-induced vasorelaxation were investigated in rabbit aortic strips. The aortic strips were pre-contracted with phenylephrine, followed by relaxation with 0.5 microM GTN, wi...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(92)90184-k

    authors： Lau DT,Benet LZ

    更新日期：1992-05-28 00:00:00

  • Modulation of eosinophil migration from bone marrow to lungs of allergic rats by nitric oxide.

    abstract：:Chronic blockade of nitric oxide (NO) synthesis attenuates the eosinophil infiltration into airways of allergic rats. This study was designed to investigate whether the inhibition of eosinophil influx to the lung of allergic rats reflects modifications in the pattern of cell mobilization from the bone marrow to periph...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2004.05.025

    authors： Ferreira HH,Costa RA,Jacheta JM,Martins AR,Medeiros MV,Macedo-Soares MF,De Luca IM,Antunes E,De Nucci G

    更新日期：2004-08-15 00:00:00