New silver(I) phosphino complexes: Evaluation of their potential as prospective agents against Mycobacterium tuberculosis

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dc.contributor.authorMaldonado, Yndira Dolores
dc.contributor.authorScalese, Gonzalo
dc.contributor.authorManieri, Karyn Fernanda [UNESP]
dc.contributor.authorPavan, Fernando R. [UNESP]
dc.contributor.authorAguirre Méndez, Larry D.
dc.contributor.authorGambino, Dinorah
dc.contributor.institutionUniversidad Nacional de Ingeniería
dc.contributor.institutionUniversidad de la República
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2022-05-01T11:07:40Z
dc.date.available2022-05-01T11:07:40Z
dc.date.issued2022-02-01
dc.description.abstractDespite being a preventable and curable disease, Tuberculosis (TB) is the world's top infectious killer. Development of new drugs is urgently needed. In this work, the synthesis and characterization of new silver(I) complexes, that include N′-[(E)-(pyridine-2-ylmethylene)pyrazine-2-carbohydrazide, HPCPH, as main ligand and substituted aryl-phosphines as auxiliary ligands, is reported. HPCPH was synthesized from pyrazinoic acid, the active metabolite of the first-line antimycobacterial drug pyrazinamide. Complexes [Ag(HPCPH)(PPh3)2]OTf (1), [Ag(HPCPH)((P(p-tolyl)3)2]OTf (2) and [Ag(HPCPH)(P(p-anisyl)3)2]OTf (3) were characterized in solid state and in solution by elemental analysis and FTIR and NMR spectroscopies (OTf[dbnd]triflate). Crystal structures of (1,2) were determined by XRD. The Ag atom is coordinated to azomethine and pyridine nitrogen atoms of HPCPH ligand and to the phosphorous atom of each aryl-phosphine co-ligand. Although HPCPH did not show activity, the Ag(I) compounds demonstrated activity against Mycobacterium tuberculosis (MTB), H37Rv strain, and multi-drug resistant clinical isolates (MDR-TB). Globally, results showed that the compounds are not only effective against the sensitive strain, but are more potent against MDR-TB than antimycobacterial drugs used in therapy. The compounds showed low to moderate selectivity index values (SI) towards the bacteria, using MRC-5 cells (ATCC CCL-171) as mammalian cell model. Interaction with DNA was explored to get insight into the potential mechanism of action against the pathogen. No significant interaction was detected, allowing to discard this biomolecule as a potential molecular target. Compound 1 was identified as a hit compound (MIC90 2.23 μM; SI 4.4) to develop further chemical modifications in the search for new drugs.en
dc.description.affiliationEscuela de Ingeniería Química Facultad de Ingeniería Química y Textil Universidad Nacional de Ingeniería
dc.description.affiliationLaboratorio de Biopolímeros y Metalofármacos LIBIPMET Facultad de Ciencias Universidad Nacional de Ingeniería
dc.description.affiliationÁrea Química Inorgánica Facultad de Química Universidad de la República
dc.description.affiliationFaculdade de Ciências Farmacêuticas UNESP
dc.description.affiliationFacultad de Ingeniería Eléctrica y Electrónica Universidad Nacional de Ingeniería
dc.description.affiliationUnespFaculdade de Ciências Farmacêuticas UNESP
dc.identifierhttp://dx.doi.org/10.1016/j.jinorgbio.2021.111683
dc.identifier.citationJournal of Inorganic Biochemistry, v. 227.
dc.identifier.doi10.1016/j.jinorgbio.2021.111683
dc.identifier.issn1873-3344
dc.identifier.issn0162-0134
dc.identifier.scopus2-s2.0-85120893195
dc.identifier.urihttp://hdl.handle.net/11449/233885
dc.language.isoeng
dc.relation.ispartofJournal of Inorganic Biochemistry
dc.sourceScopus
dc.subjectArylphosphines
dc.subjectDNA interaction
dc.subjectLipophilicity
dc.subjectMycobacterium tuberculosis
dc.subjectPyrazinoic acid derivative
dc.subjectSilver(I)
dc.titleNew silver(I) phosphino complexes: Evaluation of their potential as prospective agents against Mycobacterium tuberculosisen
dc.typeArtigo

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