Isoindolin-1-ones from the stems of Nicotiana tabacum and their antiviral activities.

Autor: Yang, Guang-Yu, Dai, Jia-Meng, Li, Zhen-Jie, Wang, Jin, Yang, Feng-Xian, Liu, Xin, Li, Jing, Gao, Qian, Li, Xue-Mei, Li, Yin-Ke, Wang, Wei-Guang, Zhou, Min, Hu, Qiu-Fen
Zdroj: Archives of Pharmacal Research; Aug2022, Vol. 45 Issue 8, p572-583, 12p
Abstrakt: In previous studies, several isoindolin-1-one analogs that exhibited significant anti-tobacco mosaic virus (anti-TMV) activities were isolated from Nicotiana tabacum. Since gene-editing mutants provide a new sample for the discovery of active metabolites, we focused on the stems of YN-18–23 (a mutant N. tabacum for gene editing with the alkaloid metabolic pathway cultivated by Yunnan Tobacco Company), which led to the isolation of four new (1–4) and four known (5–8) isoindolin-1-ones. To the best of our knowledge, nicindole C (3) is the first subclass of isoindolin-1-one bearing a pentacyclic ketone, while nicindole D (4) is the first example of isoindolin-1-one bearing a methyl-pyridin-2-(1H)-one moiety. Compounds 1–4 were tested for their anti-TMV activities, and the results revealed that compounds 1, 3, and 4 exhibited high anti-TMV activities at concentrations of 20 μM with inhibition rates of 48.6, 42.8, and 71.5%, respectively. These rates are higher than the inhibition rate of the positive control (33.2%). The mechanistic study of compound 4, which had the highest anti-TMV activity revealed that increased potentiation of defense-related enzyme activities and downregulation of expression of the NtHsp70 protein may induce resistance in tobacco against the viral pathogen TMV. Molecular docking studies also revealed that the isoindolin-1-one substructure is fundamental for anti-TMV activity. The methyl-pyridin-2-(1H)-one moiety in compound 4 and the 2-oxopropyl groups in compounds 1 and 3 at the N-2 position may increase inhibitory activities. This study of the structure–activity relationship is helpful for finding new anti-TMV activity inhibitors. To study whether the isoindolin-1-ones have broader antiviral activities, compounds 1–4 were also tested for their anti-rotavirus activities. Compound 4 exhibited high anti-rotavirus activity with a therapeutic index (TI) value of 20.7. This TI value is close to that of the positive control (20.2). [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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