RESUMEN
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) H37Rv 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 H37Rv 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.
RESUMEN
O estudo químico de Aloysia gratissima (Gillies & Hook.) Tronc. e Aloysia virgata (Ruiz & Pav.) Pers., Verbenaceae, resultou no isolamento de quatorze substâncias. Suas estruturas foram determinadas com base nos dados de IV, RMN de ¹H e de 13C uni e bidimensionais e comparação com dados da literatura. A atividade antibacteriana do extrato bruto das folhas e caules e das frações de A. virgata, bem como as substâncias hoffmaniacetona e seu monoacetato, verbascosídeo e arenariosídeo, foram avaliadas através do método de bioautografia e a atividade antiedematogênica foi avaliada pelo modelo de edema de orelha induzido para os extratos brutos e frações metanólicas de A. gratissima e A. virgata..
Phytochemical study of Aloysia gratissima (Gillies & Hook.) Tronc. e Aloysia virgata (Ruiz & Pav.) Pers., Verbenaceae, afforded fourteen compounds. The structures were established using IR, 1D and 2D NMR and by comparison of its spectroscopic data to those of literature. The antibacterial activity of the crude extract from the leaves and branches and the fractions from the crude extract of A. virgata, besides the isolated compounds hoffmaniacetone, hoffmaniacetone monoacetate, verbascoside and arenarioside were evaluated by means of bioautography and the antiedematogenic activity was evaluated using induced ear oedema model to the crude extracts and methanol fractions for A. gratissima and A. virgata.