RESUMEN
An artificial series of macrocycles based on 4,4'-sulfonyldiphenol intermediate was synthesized using a multistep procedure involving oxidation of bisphenol sulfide, etherification of phenolic hydroxyl groups, and final ring closure with different diamines. Different chemical species having aromatic, heteroaromatic, and aliphatic characters were incorporated into macrocyclic frameworks in the final step of ring closure. This simple and easily executable synthetic strategy was applied to synthesize 15 macrocycles (5a-o) in excellent yields. Characterization of the synthesized products was achieved through well-known modern spectroscopic techniques such as IR, NMR, and Mass. Macrocycles 5m and 5n were found to show significant AChE inhibition with IC50 values of 76.9 ± 0.24 and 71.2 ± 0.77 µM, respectively. Macrocycle 5n was also found to be an active inhibitor of butyrylcholinesterase (BChE) with IC50 score of 55.3 ± 0.54 µM. Among others, macrocycle 5l cyclized with o-phenylenediamine demonstrated moderate inhibition with IC50 value of 81.1 ± 0.54 µM. Increasing interest in studying interactions of macrocycles with different enzymatic targets compelled us to design and synthesize sulfone-based macrocycles that might prove as highly potent class of biologically active compounds.
Asunto(s)
Inhibidores de la Colinesterasa/síntesis química , Compuestos Macrocíclicos/síntesis química , Simulación del Acoplamiento Molecular , Sulfonas/química , Enfermedad de Alzheimer/tratamiento farmacológico , Estructura Molecular , Relación Estructura-ActividadRESUMEN
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
Sclerotinia sclerotiorum is responsible for the white mold of soybeans, and the difficulty to control the disease in Brazil is causing million-dollar damages. Stachybotrys levispora has shown activity against S. sclerotiorum. In our present investigation, we analyzed the chemical basis of this inhibition. Eight compounds were isolated, and using spectroscopic methods, we identified their structures as the known substances 7-dechlorogriseofulvin, 7-dechlorodehydrogriseofulvin, griseofulvin, dehydrogriseofulvin, 3,13-dihydroxy-5,9,11-trimethoxy-1-methylbenzophenone, griseophenone A, 13-hydroxy-3,5,9,11-tetramethoxy-1-methylbenzophenone, and 12-chloro-13-hydroxy-3,5,9,11-tetramethoxy-1-methylbenzophenone. Griseofulvin inhibited the mycelial growth of S. sclerotiorum at 2 µg mL-1. Thus, the antagonistic effect of S. levispora to S. sclerotiorum may well be due to the presence of griseofulvins. Our results stimulate new work on the biosynthesis of griseofulvins, to locate genes that encode key enzymes in these routes and use them to increase the production of these compounds and thus potentiate the fungicide effect of this fungus. S. levispora represents an agent for biocontrol, and griseofulvin represents a fungicide to S. sclerotiorum.