Preclinical tests for salicylhydrazones derivatives to explore their potential for new antituberculosis agents.

Autor: Ieque AL; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Paraná, 87020-900, Brazil. Electronic address: andressa_ieque@hotmail.com., Palomo CT; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Paraná, 87020-900, Brazil. Electronic address: trevisollicarolina@gmail.com., Gabriela de Freitas Spanhol V; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Paraná, 87020-900, Brazil. Electronic address: vitoriafreitas557@gmail.com., Fróes da Motta Dacome ML; Postgraduate Program in Bioscience and Physiopathology, State University of Maringá, Maringá, Paraná, 87020-900, Brazil. Electronic address: marialuizafroes1704@gmail.com., Júnior do Carmo Pereira J; Departament of Chemistry - Federal Institute of Paraná, Paranavaí, Paraná, 87703-536, Brazil. Electronic address: jjcpereira30@hotmail.com., Candido FC; Departament of Chemistry - Federal Institute of Paraná, Paranavaí, Paraná, 87703-536, Brazil. Electronic address: fran_ciellilinda@hotmail.com., Caleffi-Ferracioli KR; Postgraduate Program in Bioscience and Physiopathology, State University of Maringá, Maringá, Paraná, 87020-900, Brazil; Laboratory of Medical Bacteriology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, 87020-900, Brazil. Electronic address: katianyrcf@gmail.com., Dias Siqueira VL; Postgraduate Program in Bioscience and Physiopathology, State University of Maringá, Maringá, Paraná, 87020-900, Brazil; Laboratory of Medical Bacteriology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, 87020-900, Brazil. Electronic address: vldsiqueira@uem.br., Cardoso RF; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Paraná, 87020-900, Brazil; Postgraduate Program in Bioscience and Physiopathology, State University of Maringá, Maringá, Paraná, 87020-900, Brazil; Laboratory of Medical Bacteriology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, 87020-900, Brazil. Electronic address: rfcardoso@uem.br., Vandresen F; Departament of Chemistry, Federal Technological University of Paraná, Londrina, Paraná, 86036-370, Brazil. Electronic address: fvandresen@hotmail.com., Alves-Olher VG; Departament of Chemistry - Federal Institute of Paraná, Paranavaí, Paraná, 87703-536, Brazil. Electronic address: vanessa.olher@ifpr.edu.br., de Lima Scodro RB; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Paraná, 87020-900, Brazil; Laboratory of Medical Bacteriology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, 87020-900, Brazil. Electronic address: rblscodro@uem.br.
Jazyk: angličtina
Zdroj: Tuberculosis (Edinburgh, Scotland) [Tuberculosis (Edinb)] 2024 Sep; Vol. 148, pp. 102545. Date of Electronic Publication: 2024 Jul 16.
DOI: 10.1016/j.tube.2024.102545
Abstrakt: Purpose: This study target the synthesis of 22 salicylhydrazones derivatives to apply in vitro screening to explore their potential in the search for new anti-TB prototypes drugs.
Methods: The minimum inhibitory concentration (MIC) were evaluated against Mycobacterium tuberculosis (Mtb) H 37 Rv and clinical isolates. Drug combination assay, cytotoxicity assay, ethidium bromide accumulation assay (EtBr) and in silico analysis regarding the absorption, distribution, metabolism, excretion and toxicity (ADMET) and pharmacological properties were also performed.
Results: Three most promising compounds were selected (10, 11 and 18) to proceed with screening tests. Compound 18 presented the lowest MIC value (0.49 μg/mL) against Mtb H 37 Rv strain, followed by compounds 11 (3.9 μg/mL) and 10 (7.8 μg/mL). All compounds showed activity against drug susceptible and resistant clinical isolates. Cytotoxicity results were promising for all salicylhydrazones, with SI values up to 4,205 for compound 18. The derivative 10 was the only one that demonstrated a non-promising cytotoxicity scenario for a single cell line. All derivatives showed an additive effect (FICI >0.5 to 4.0) in combination with isoniazid, ethambutol and rifampicin.
Conclusion: All salicylhydrazones showed potential in the screening tests performed in this study and compound 18 stood out due to its activity against susceptible and resistant bacilli at low concentrations and low cytotoxicity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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