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Thomson Walt (คุย | ส่วนร่วม)
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=[[ไนโตรโซลีน]]=
=[[ยาปฏิชีวนะ]]=▼
{{Drugbox
=== Pared celular ===
| Verifiedfields = changed
Algunos antibióticos ejercen su función en regiones y [[orgánulo]]s intracelulares, por lo que son ineficaces en bacterias que contengan una pared celular, a menos que se logre inhibir la síntesis de esta estructura exterior, presente en muchas bacterias, pero no en [[animal]]es. Muchos antibióticos van dirigidos a bloquear la síntesis, exportación, organización o formación de la pared celular, específicamente los enlaces cruzados del [[peptidoglicano]], el principal componente de la pared celular, sin interferir con los componentes intracelulares.<ref name="harrison" /> Esto permite alterar la composición intracelular del microorganismo por medio de la [[presión osmótica]]. Como la maquinaria intracelular permanece intacta, ello aumenta la presión interna sobre la membrana hasta el punto en que ésta cede, el contenido celular se libera al exterior, y la bacteria muere. También permiten la entrada de otros agentes [[:Categoría:Antiinfecciosos|antimicrobianos]] que no pueden atravesar la pared celular.<ref name="encarta" /> Algunos ejemplos clásicos son:
| verifiedrevid = 462262233
| IUPAC_name = 5-nitroquinolin-8-ol
| image = nitroxoline.png
| width = 120px
 
<!--Clinical data-->
* la [[bacitracina]]: del grupo de los péptidos, inhibe al transportador [[lípido|lipídico]] del peptidoglucano hacia el exterior de la célula.
| tradename =
* la [[penicilina]]: en el grupo de los betalactámicos, inhibe la transpeptidación, una reacción en la que se producen los enlaces cruzados de la pared celular y bloquea los inhibidores de las autolisinas.
| Drugs.com = {{drugs.com|international|nitroxoline}}
* las [[cefalosporina]]s: otro tipo de moléculas que inhiben la transpeptidación, por unión a las proteínas PBPs, implicadas en la última fase de la formación de la pared celular.
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
| routes_of_administration =
 
<!--Pharmacokinetic data-->
=== Membrana celular ===
| bioavailability =
Ciertos antibióticos pueden lesionar directa o indirectamente —al inhibir la síntesis de los constituyentes— la integridad de la [[membrana celular]] de las bacterias y de ciertos [[hongo]]s. Las [[polimixina]]s, por ejemplo, son antibióticos que actúan como [[surfactante]] o [[detergente]] que reacciona con los [[lípido]]s de la [[membrana celular]] de las bacterias. Ello destruye la integridad de la permeabilidad de la membrana. Los elementos hidrosolubles y algunos que son tóxicos para el germen, pueden así entrar sin restricción al interior celular.<ref name="harrison" /> La [[gramicidina A]] forma poros o canales en las bicapas lipídicas.
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
 
<!--Identifiers-->
=== Acción sobre ácidos nucleicos (ADN y ARN) y proteínas ===
| CAS_number_Ref = {{cascite|correct|??}}
Algunos antibióticos actúan bloqueando la síntesis del [[ADN]], [[ARN]], [[ribosoma]]s, [[ácido nucleico|ácidos nucleicos]] o las [[enzima]]s que participan en la síntesis de las [[proteína]]s, resultando en proteínas defectuosas.<ref name="encarta" /> La [[mitomicina]] es un compuesto con estructura asimétrica y que se fija a las hélices del ADN e inhibe o bloquea la expresión de la [[enzima]] [[ADN polimerasa]] y, por ende, la replicación del ADN y el ensamblaje de las proteínas. La [[actinomicina]], por su parte, ejerce su mecanismo en la misma manera que la mitomicina, solo que es una molécula simétrica.
| CAS_number = 4008-48-4
| ATC_prefix = J01
| ATC_suffix = XX07
| PubChem = 19910
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01422
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 18756
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = A8M33244M6
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07245
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1454910
 
<!--Chemical data-->
Las [[sulfamida]]s son análogos estructurales de [[molécula]]s biológicas y tienen parecido a las moléculas normalmente usadas por la [[célula]] diana. Al hacer uso de estas moléculas farmacológicas, las vías metabólicas del microorganismo son bloqueadas, provocando una inhibición en la producción de [[base nitrogenada|bases nitrogenadas]] y, eventualmente, la muerte celular.
| C=9 | H=6 | N=2 | O=3
| molecular_weight = 190.156 g/mol
| smiles = [O-][N+](=O)c1ccc(O)c2ncccc12
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C9H6N2O3/c12-8-4-3-7(11(13)14)6-2-1-5-10-9(6)8/h1-5,12H
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RJIWZDNTCBHXAL-UHFFFAOYSA-N
}}
 
'''Nitroxoline''' is an [[antibiotic]]<ref name="pmid7793877">{{cite journal |authors=Pelletier C, Prognon P, Bourlioux P |title=Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains |journal=Antimicrob. Agents Chemother. |volume=39 |issue=3 |pages=707–13 |year=1995 |pmid=7793877 |doi= 10.1128/aac.39.3.707|url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=7793877 |pmc=162609}}</ref> that has been in use in Europe for about fifty years, and has proven to be very effective at combating [[biofilm]] infections. Nitroxoline was shown to cause a decrease in the biofilm density of ''[[P. aeruginosa]]'' infections, which would allow access to the infection by the immune system ''in vivo''.<ref>{{cite journal |authors=Sobke A, Klinger M, Hermann B, Sachse S, Nietzsche S, Makarewicz O, Keller PM, Pfister W, Straube E |title=The Urinary Antibiotic 5-Nitro-8-Hydroxyquinoline (Nitroxoline) Reduces the Formation and Induces the Dispersal of Pseudomonas aeruginosa Biofilms by Chelation of Iron and Zinc |journal=Antimicrob. Agents Chemother. |volume=56 |pages=6021–6025 |year=2012 |url=http://aac.asm.org/content/56/11/6021 |issue=11 |doi=10.1128/aac.01484-12 |pmid=22926564 |pmc=3486607}}</ref> It was shown that nitroxoline functions by [[chelating]] Fe<sup>2+</sup> and Zn<sup>2+</sup> ions from the biofilm matrix; when Fe<sup>2+</sup> and Zn<sup>2+</sup> were reintroduced into the system, biofilm formation was reconstituted. The activity of biofilm degradation is comparable to [[EDTA]], but has a history of human use in clinical settings and therefore has a precedent with which to allow its use against “slimy” biofilm infections.
Las [[quinolona]]s y [[fluoroquinolona]]s actúan sobre enzimas bacterianas del tipo [[girasa]]s y [[topoisomerasa]]s del ADN, responsables de la topología de los [[cromosoma]]s, alterando el control celular sobre la replicación bacteriana y produciendo una alteración en la lectura del mensaje [[gen]]ético.<ref name="harrison" />
 
==Anticancer Activity==
=== Acción sobre los ribosomas ===
The chelating activities of nitroxoline have also been used in an anticancer setting. Nitroxoline has been shown to be more [[cytotoxic]] to [[HL60]], DHL-4, Panc-1, and A2780 cells lines than [[clioquinol]] and other [[8-hydroxyquinoline]] derivatives.<ref>{{cite journal |authors=Jiang H, Taggart JE, Zhang X, Benbrook DM, Lind SE, Ding W |title=Nitroxoline (8-hydroxy-5-nitroquinoline) is more a potent anti-cancer agent than clioquinol (5-chloro-7-iodo-8-quinoline) |journal=Cancer Lett |volume=312 |pages=11–17 |year=2011 |pmc=3395224 |doi=10.1016/j.canlet.2011.06.032 |pmid=21899946 |issue=1}}</ref> It also demonstrated an increase in [[reactive oxygen species]] (ROS) production over controls, especially when Cu<sup>2+</sup> was added. The ROS levels reached over 350% of the controls with addition of CuCl<sub>2</sub>. Interestingly, the cytotoxicity production was markedly decreased with addition of ZnCl<sub>2</sub>, indicating, based on this model, that nitroxoline is not a zinc chelator. Because the zinc chelating action of clioquinol has been associated with [[subacute myelo-optic neuropathy]], the use of nitroxoline as a cytotoxic drug in the treatment of cancers should not exhibit neurotoxic effects in humans, and ''in vivo'' trials on tumour xenografts in mice have not yielded any negative neurodegenerative effects.
Aproximadamente la mitad de los antibióticos actúan por inhibición de los [[ribosoma]]s bacterianos, los orgánulos responsables de la síntesis de proteínas y que son distintos en composición de los ribosomas en mamíferos. Algunos ejemplos incluyen los [[aminoglucósido]]s (se unen de forma irreversible a la subunidad 30S del ribosoma), las [[tetraciclina]]s (bloquean la unión del [[aminoacil ARNt]] al complejo [[ARNm]]-ribosoma), [[eritromicina]] (se fijan de manera específica a la porción 50S de los ribosomas bacterianos) y la [[doxiciclina]].<ref name="harrison" />
 
Nitroxoline has been shown to [[Enzyme inhibitor|inhibit the enzymatic activity]] of [[cathepsin B]].<ref>{{cite journal |authors=Mirkovic B, Renko M, Turk S, Sosic I, Jevnikar Z, Obermajer N, Turk D, Gobec S, Kos J |title=Novel Mechanism of Cathepsin B Inhibition by Antibiotic Nitroxoline and Related Compounds |journal=ChemMedChem |volume=6 |pages=1351–1356 |year=2011 |doi=10.1002/cmdc.201100098}}</ref> Cathepsin B degrades extra-cellular membrane proteins in tumor cells, allowing them to proliferate more freely, and metastasize throughout the body. Nitroxoline was shown to be a noncompetitive, reversible inhibitor of these actions in MCF-10A neoT cells. The ''K''<sub>i</sub> ([[dissociation constant]]) values it demonstrates are comparable to other reversible inhibitors of cathepsin B. This indicates that it may be a candidate for further trials as an anticancer drug, especially given its history as an antimicrobial agent and its well-known [[pharmacokinetic]] profile. The mechanism of action by which nitroxoline inhibits cathepsin B may also suggest that further research of noncovalent, noncompetitive inhibitors of cathepsin B could be warranted. In fact, it was recently shown that a balance exists between the potency and the kinetics of a molecule, reflected in the molecular weight, which must be optimized in order to create the best drug for inhibition of a target enzyme.<ref>{{cite journal |authors=Sosic I, Mirkovic B, Arenz K, Stefane B, Kos J, Gobec S |title=Development of New Cathepsin B Inhibitors: Combining Bioisosteric Replacements and Structure-Based Design To Explore the Structure-Activity Relationships of Nitroxoline Derivatives |journal=J Med Chem |volume=56 |pages=521–533 |year=2013 |url=http://pubs.acs.org/doi/abs/10.1021/jm301544x |doi=10.1021/jm301544x}}</ref> For example, a certain inhibitor may have a high affinity for an enzyme, but it may prove impractical to use in a clinical setting for treatment because of its size.
 
Nitroxoline and its analogues have also been shown to have [[antiangiogenic]] properties.<ref name="doi=10.1093/jnci/djq457">{{cite journal |author=Joong Sup Shim, Yoshiyuki Matsui, Shridhar Bhat, Benjamin A. Nacev, Jing Xu, Hyo-eun CB, Surajit Dhara, Kee Chung Han, Curtis R. Chong, Martin G. Pomper, Alan So Jun O. Liu |title=Effect of Nitroxoline on Angiogenesis and Growth of Human Bladder Cancer |journal=J Natl Cancer Inst |volume=102 |issue=24 |pages=1855–1873 |year=2010 |doi=10.1093/jnci/djq457 |url=http://jnci.oxfordjournals.org/content/102/24/1855.full |pmid=21088277 |pmc=3001967}}</ref> For example, nitroxoline inhibits [[METAP2|MetAP2]] activity, an enzyme associated with [[angiogenesis]], and [[HUVEC]] proliferation.<ref>{{cite journal |authors=Bhat S, Shim JS, Zhang F, Chong CR, Liu JO |title=Substituted oxines inhibit endothelial cell proliferation and angiogenesis |journal=Org Biomol Chem. |volume=10 |pages=2979–2992 |year=2012 |doi=10.1039/C2OB06978D |url=http://pubs.rsc.org/en/Content/ArticleLanding/2012/OB/c2ob06978d}}</ref> This is further evidence that nitroxoline would make an effective anticancer drug. With different derivatives of nitroxoline demonstrating various levels of inhibition, nitroxoline may also prove to be a novel starting point for future research into cancer treatment.
 
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