RESUMEN
In natural product studies, the purification of metabolites is an important challenge. To accelerate this step, alternatives such as integrated analytical tools should be employed. Based on this, the chemical study of Swinglea glutinosa (Rutaceae) was performed using two rapid dereplication strategies: Target Analysis (Bruker Daltonics®, Bremen, Germany) MS data analysis combined with MS/MS data obtained from the GNPS platform. Through UHPLC-HRMS data, the first approach allowed, from crude fractions, a quick and visual identification of compounds already reported in the Swinglea genus. Aside from this, by grouping compounds according to their fragmentation patterns, the second approach enabled the detection of eight molecular families, which presented matches for acridonic alkaloids, phenylacrylamides, and flavonoids. Unrelated compounds for S. glutinosa have been isolated and characterized by NMR experiments, Lansamide I, Lansiumamide B, Lansiumamide C, and N-(2-phenylethyl)cinnamamide.
Asunto(s)
Acridonas/análisis , Acrilamidas/análisis , Metabolómica/métodos , Rutaceae/química , Cromatografía Líquida de Alta Presión , Cinamatos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Metabolismo Secundario , Estirenos/aislamiento & purificaciónRESUMEN
Symmetrical and unsymmetrical bis-aryl-α,ß-unsaturated ketones were synthesized in moderate to excellent yield by treating cyclohexanone with various aldehydes. Dimethylammonium dimethylcarbamate (DIMCARB) was used as both catalyst and reaction medium for the synthesis of monoarylidenes cycloadduct intermediates, which was further used to produce diarylidene cyclohexanones. All the 34 compounds synthesized were evaluated for their anti-proliferative activity, particularly against promastigote of Leishmania amazonensis, epimastigoteand trypomastigoteof Trypanosoma cruzi. Eighteen compounds displayed anti-leishmanial activity against promastigotes of L. amazonensis with IC50 values ranging from 2.8 to 10⯵M. In addition, two compounds exhibited significant antitrypanosomal activity against epimastigotes of T. cruzi with IC50 values of 5.2⯱â¯0.8 and 3.0⯱â¯0.0⯵M, while five compounds exhibited activity from 15.0⯱â¯1.4 to 30.2⯱â¯1.8⯵M against trypomastigote of T. cruzi. Moreover, all compounds were more selective against the parasites than the epithelial cells. The unsymmetrical compounds 16, 28, 30 and 33 can be considered as favorable anti-parasitic lead molecule having IC50 and EC50 values in the low-micromolar range, better than the reference drug benznidazole, and low cytotoxicity against Vero cells. The potent compounds were screened in silico against 17 enzymes of T. cruzi and best scoring were found against Dihydroorotate Dehydrogenase.