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

Autor: Maldonado YD; Escuela de Ingeniería Química, Facultad de Ingeniería Química y Textil, Universidad Nacional de Ingeniería, Lima, Peru; Laboratorio de Biopolímeros y Metalofármacos, LIBIPMET, Facultad de Ciencias, Universidad Nacional de Ingeniería, Lima, Peru., Scalese G; Área Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay., Manieri KF; Faculdade de Ciências Farmacêuticas, UNESP, Araraquara, Brazil., Pavan FR; Faculdade de Ciências Farmacêuticas, UNESP, Araraquara, Brazil., Aguirre Méndez LD; Laboratorio de Biopolímeros y Metalofármacos, LIBIPMET, Facultad de Ciencias, Universidad Nacional de Ingeniería, Lima, Peru; Facultad de Ingeniería Eléctrica y Electrónica, Universidad Nacional de Ingeniería, Lima, Peru., Gambino D; Área Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay. Electronic address: dgambino@fq.edu.uy.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2022 Feb; Vol. 227, pp. 111683. Date of Electronic Publication: 2021 Dec 03.
DOI: 10.1016/j.jinorgbio.2021.111683
Abstrakt: 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)(PPh 3 ) 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 (OTftriflate). 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), H 37 Rv 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 (MIC 90 2.23 μM; SI 4.4) to develop further chemical modifications in the search for new drugs.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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