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

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Título

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

Tema

PLATA
TUBERCULOSIS
FARMACOS
BIBLIOGRAFIA NACIONAL QUIMICA
2022

Abstract

Despite 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––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 multidrug 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.

Autor

Maldonado, Yndira Dolores
Manieri, Karyn Fernanda
Pavan, Fernando R.
Aguirre Méndez, Larry D.

Fuente

Journal of Inorganic Biochemistry v. 227, 2022. -- e111683

Editor

Elsevier

Fecha

2022

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PDF

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Inglés

Tipo

Artículo

Identificador

10.1016/j.jinorgbio.2021.111683

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Original Format

PDF
Fecha de agregación
May 20, 2022
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
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Citación
Maldonado, Yndira Dolores, “New silver(I) phosphino complexes : evaluation of their potential as prospective agents against Mycobacterium tuberculosis,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed September 27, 2022, http://riquim.fq.edu.uy/items/show/6503.
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