Anti-Virus Isoindolinone alkaloids with rare oxocyclopenta[f]isoindole frameworks isolated from the stems of flue cured tobacco

Abstract

Background The large scale tobacco planting in Yunnan produces a large amount of waste, including stems, roots, low grade and defective tobacco leaves. Therefore, the multipurpose utilization of the by-product of tobacco is an interesting topic. In order to increase medicinal value of tobacco and the comprehensive utilization of its by-products, our group had investigated the chemical constituents of the stems of Y-202, a cultivar of tobacco with high resistance to tobacco mosaic virus (TMV), which originated from K326 by ethylmethane sulfonate (EMS) mutagenesis. Results As a result, four new isoindolinone-type small molecule alkaloids named nicoisoindoles A–D (1–4), along with four known isoindole derivatives (5–8) were isolated. Nicoisoindoles A–D represent a new subclass of isoindolinone alkaloids with rare cyclopenta[f]isoindole-1-one frameworks. Among them, nicoisoindole C (3) possesses an unusual N-2-(5-methoxy-6-methylpyridin-2-yl)ethyl moiety, while nicoisoindole D (4) has a novel a N-(3-methyl-6-oxo-1,6-dihydropyridin-2-yl)methyl substituent. Interestingly, compounds 1, 3, and 4 showed high anti-TMV activities with inhibition rates of 43.8, 58.8, and 67.8% at the concentration of 20 µM, and IC50 values of 23.6, 19.5 and 15.4 µM, respectively, even more potent than that of positive control. In order to study whether the oxocyclopenta[f]isoindole-1-ones have more broad antiviral activities, compounds 1–4 were also tested for their anti-rotavirus activities, and they exhibited potential anti-rotavirus activities with therapeutic index (TI) valves in the range of 13.0-18.5. Conclusions The successful isolation and structure identification of oxocyclopenta[f]isoindole-1-ones provide materials for the screening of anti-virus activities inhibitors, and also contribute to the development and utilization of the waste from tobacco cultivation.