Abstract：
:We synthesized a novel platinum drug, cis-[PtCl(NH3)2(N7-ACV)]+, in which ACV is the antiviral drug acyclovir [a deoxyriboguanosine analogue, 9-(2-hydroxyethoxymethyl)guanine]. This new compound exhibits antiviral efficacy in vitro and exhibits an antitumor activity profile different from that of cisplatin [Metal-Based Drugs 2:249-256 (1995)]. To contribute to understanding the mechanisms underlying biological activity of this new compound, we studied modifications of natural and synthetic DNAs in cell-free media by cis-[PtCl(NH3)2(N7-ACV)]+ by various biochemical and biophysical methods. The results indicated that the major DNA adduct of cis-[PtCl(NH3)2(N7-ACV)]+ was a stable monofunctional adduct at guanine residues. In contrast to DNA adducts of other monodentate and clinically ineffective platinum(II) compounds, the adducts of cis-[PtCl(NH3)2(N7-ACV)]+ terminated in vitro DNA and RNA synthesis. In addition, although DNA adducts of cis-[PtCl(NH3)2(N7-ACV)]+ and cisplatin were different, some properties of DNA modified by either compound were qualitatively similar. Such similarities were not noticed if DNA modifications by other ineffective monofunctional platinum(II) complexes were investigated. Thus, the DNA binding mode of monofunctional cis-[PtCl(NH3)2(N7-ACV)]+ was different from that of other monofunctional but ineffective platinum(II) complexes. It has been suggested that the unique capability of cis-[PtCl(NH3)2(N7-ACV)]+ to modify DNA may be relevant to a distinct antitumor efficiency of this novel drug in comparison with cisplatin. It also has been suggested that at least some aspects of DNA interactions of cis-[PtCl(NH3)2(ACV)]+ revealed in the current study could be exploited in the search for and development of new antiviral platinum complexes containing, as a part of the coordination sphere, antiviral nucleosides.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Balcarová Z,Kaspárková J,Zákovská A,Nováková O,Sivo MF,Natile G,Brabec Vsubject
Has Abstractpub_date
1998-05-01 00:00:00pages
846-55issue
5eissn
0026-895Xissn
1521-0111journal_volume
53pub_type
杂志文章abstract：:The presence of DNA damage initiates signaling through the ataxia-telangiectasia mutated kinase (ATM) and the ATM- and the Rad3-related kinase (ATR), which phosphorylate, thus activating, the checkpoint kinases (Chk) 1 and 2, which leads to cell cycle arrest. The bifunctional DNA alkylator 1,3-bis(2-chloroethyl)-1-nit...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.053124
更新日期：2009-06-01 00:00:00
abstract：:We have identified alpha 2-adrenergic receptors on human erythroleukemia (HEL) cells, a suspension-grown cell line related to human platelets. properties of receptors were assessed in intact cells by binding of the antagonist [3H]yohimbine and by inhibition of cAMP accumulation. [3H]Yohimbine labeled 5900 +/- 2100 rec...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
abstract：:Guanine nucleotide-binding proteins (G proteins) transduce signals from agonist- and light-sensitive receptors. In the visual excitation system, the photon receptor rhodopsin is coupled to the G protein Gt (transducin). Gt is composed of alpha, beta, and gamma subunits; the alpha subunit binds guanine nucleotide, wher...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：:Bioassay-guided fractionation was used to isolate the lignan polygamain as the microtubule-active constituent in the crude extract of the Mountain torchwood, Amyris madrensis. Similar to the effects of the crude plant extract, polygamain caused dose-dependent loss of cellular microtubules and the formation of aberrant...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.075838
更新日期：2012-03-01 00:00:00
abstract：:Nitric oxide (NO) possesses potent anti-inflammatory properties; however, an over-production of NO will promote inflammation and induce cell and tissue dysfunction. Thus, the ability to precisely regulate NO production could prove beneficial in controlling damage. In this study, advantage was taken of the well charact...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.4.939
更新日期：2001-04-01 00:00:00
abstract：:The effect of lysosomotropic agents and secretory inhibitors were compared with verapamil for their effect on the activity of doxorubicin (DOX) in multiple drug-resistant (MDR) P388 leukemia cells (P388R) and in blocking anthracycline efflux from these cells. Agents known to interact with the plasma membrane did not p...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:Up-regulation of fractalkine is involved in vascular and tissue damage in inflammatory conditions. Resveratrol has been shown to have anti-inflammatory, antioxidant, and antitumor activities. Its regulatory effects on expression of fractalkine in vascular endothelial cells and fractalkine receptor CX3CR1 in monocytes ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.022392
更新日期：2006-07-01 00:00:00
abstract：:(+/-)-6' beta-Fluoroaristeromycin (F-C-Ado) is a potent and competitive inhibitor of purified S-adenosylhomocysteine (AdoHcy) hydrolase isolated from murine L929 cells (Ki = 3.1 nM). It also inhibits vaccinia virus and vesicular stomatitis virus replication in L929 cells, at a 90% inhibitory dose (ID90) of 3.5 and 13 ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-06-01 00:00:00
abstract：:The chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) shows potent and selective anticancer and antimetastatic activity. However, the mechanism by which it is initially transported into cells to induce cytotoxicity is unknown. Hence, the current investigation examined the cellular uptake of ¹⁴C-Dp4...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.088393
更新日期：2013-12-01 00:00:00
abstract：:Chronic stimulation of beta-adrenoceptors leads to increased mRNA and protein levels of pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in the heart. In the present study the time course is reported of the effect of isoprenaline infusions on myocardial mRNA levels of Gi alpha-2, Gi alp...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:The effect of the neuromuscular blocker alcuronium on the binding of N-[3H]-methylscopolamine [( 3H]NMS) and l-[3H]quinuclidinylbenzilate ([3H]QNB) to muscarinic binding sites in rat heart atria, longitudinal smooth muscle of the ileum, cerebral cortex, cerebellum, and submaxillary glands was measured using filtration...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:Past decades of cancer research have mainly focused on the role of various extracellular and intracellular biochemical signals on cancer progression and metastasis. Recent studies suggest an important role of mechanical forces in regulating cellular behaviors. This review first provides an overview of the mechanobiolo...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.116.106765
更新日期：2016-12-01 00:00:00
abstract：:The nicotinic acetylcholine receptor can be expressed in Xenopus oocytes by injection of in vitro synthesized RNA for the alpha, beta, gamma, and delta mouse muscle subunits. However, detectable responses can also be obtained by injection of alpha, beta, and delta subunit RNA only. The receptors expressed in this case...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-04-01 00:00:00
abstract：:To study behavior of activated G(alpha)(s) in living cells, green fluorescent protein (GFP) was inserted within the internal amino acid sequence of G(alpha)(s) to generate a G(alpha)(s)-GFP fusion protein. The fusion protein maintained a bright green fluorescence and was identified by immunoblotting with antibodies ag...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.2.352
更新日期：2002-02-01 00:00:00
abstract：:Prolonged ethanol exposure causes central nervous system hyperexcitability that involves a loss of GABAergic inhibition. We previously demonstrated that long-term ethanol exposure enhances the internalization of synaptic GABA(A) receptors composed of alpha1beta2/3gamma2 subunits. However, the mechanisms of ethanol-med...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.063016
更新日期：2010-05-01 00:00:00
abstract：:Consequent to agonist exposure, many G protein-coupled receptors undergo sequestration or internalization. Results with receptors linked to adenylate cyclase, such as the beta 2-adrenergic receptor, or receptors linked to phospholipase C (PLC) have provided conflicting results regarding the role of second messenger-de...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:Na+-d-glucose cotransporter 1 (SGLT1) is rate-limiting for glucose absorption in the small intestine. Shortly after intake of glucose-rich food, SGLT1 abundance in the luminal membrane of the small intestine is increased. This upregulation occurs via glucose-induced acceleration of the release of SGLT1-containing vesi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.104521
更新日期：2016-11-01 00:00:00
abstract：:The firmest candidate among the transmembrane portions of the nicotinic acetylcholine receptor (AChR) to be in contact with the lipid bilayer is the fourth segment, M4. To explore the contribution of alphaM4 amino acid residues of mouse AChR to channel gating, we combined site-directed mutagenesis with single-channel ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.54.1.146
更新日期：1998-07-01 00:00:00
abstract：:Based on the available data, we speculated that changes in brain iron metabolism induced by L-DOPA might be associated with the neurotoxicity of L-DOPA. To investigate this possibility, the effects of L-DOPA on the expression of iron influx proteins [transferrin receptor (TfR) and divalent metal transporter 1 (DMT1)],...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.017756
更新日期：2006-03-01 00:00:00
abstract：:A variety of direct and indirect techniques have revealed the existence of ATP-sensitive potassium (KATP) channels in the inner membranes of mitochondria. The molecular identity of these mitochondrial KATP (mitoKATP) channels remains unclear. We used a pharmacological approach to distinguish mitoKATP channels from cla...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-06-01 00:00:00
abstract：:Inhibitors of the serotonin transporter (SERT) are widely used antidepressant agents, but the structural mechanism for inhibitory activity and selectivity over the closely related norepinephrine transporter (NET) is not well understood. Here we use a combination of chemical, biological, and computational methods to de...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.091249
更新日期：2014-05-01 00:00:00
abstract：:A nonnaturally occurring L-configuration nucleoside analog, L-beta-5-bromovinyl-(2-hydroxymethyl)-1,3-(dioxolanyl)uracil (L-BVOddU) selectively inhibited varicella-zoster virus growth in human embryonic lung (HEL) 299 cell culture with an EC(50) of 0.055 microM, whereas no inhibition of CEM and HEL 299 cell growth or ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.5.1109
更新日期：2000-11-01 00:00:00
abstract：:Bupropion is an atypical antidepressant that also has usefulness as a smoking-cessation aid. Because hydroxybupropion, a major metabolite of bupropion, is believed to contribute to its antidepressant activity, this metabolite may also contribute to the smoking-cessation properties of bupropion. This study investigated...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.001313
更新日期：2004-09-01 00:00:00
abstract：:Serotonin 5-HT(2B) receptors are often coexpressed with 5-HT(1B) receptors, and cross-talk between the two receptors has been reported in various cell types. However, many mechanistic details underlying 5-HT(1B) and 5-HT(2B) receptor cross-talk have not been elucidated. We hypothesized that 5-HT(2B) and 5-HT(1B) recep...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.032656
更新日期：2007-06-01 00:00:00
abstract：:Molecular cloning of membrane-spanning mammalian adenylyl cyclases (ACs) has led to the discovery of nine different isotypes, making ACs potentially useful therapeutic targets. This study investigated the mechanism by which fungicidal nitroimidazole compounds modulate AC activity. Current evidence indicates that biolo...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.3.624
更新日期：2003-03-01 00:00:00
abstract：:The blocking effects of guanethidine on electrically induced, neurally mediated, contractions of the guinea pig vas deferens in vitro could be markedly antagonized by the bee venom polypeptide apamin (20-60 nM), by 0.1 mM methylene blue, and (less regularly) by 0.1-0.15 mM quinine, three substances known to inhibit ca...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:Previous studies have shown that exposure of phenobarbital-pretreated rats to halothane in 10% O2 causes centrilobular necrosis, induces expression of the 72-kDa heat shock protein (HSP72), and produces several trifluoroacetylated adducts. In the present study the time course of development of the centrilobular lesion...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:Most anticancer drugs have their origin in traditional medicinal plants. We describe here a flavone, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF), from the leaves of the Thai plant Gardenia obtusifolia, that has anti-inflammatory and anticancer potential. Because the nuclear factor-κB (NF-κB) pathway is linked ...
journal_title：Molecular pharmacology
pub_type： 杂志文章,收录出版
doi：10.1124/mol.110.067512
更新日期：2011-02-01 00:00:00
abstract：:beta-arrestins have been shown to play important roles in regulation of signaling and desensitization of opioid receptors in many in vivo studies. The current study was carried out to measure the direct interaction of beta-arrestins with two functional intracellular domains, the third intracellular loop (I3L) and the ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.4.758
更新日期：2001-04-01 00:00:00
abstract：:The endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) bind to G protein-coupled central and peripheral cannabinoid receptors CB1 and CB2, respectively. Due to the relatively high expression of the CB2 isotype on peripheral immune cells, it has been hypothesized that this receptor mediates the immunosuppres...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-05-01 00:00:00
