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).

Guang-Yu Yang

Jia-Meng Dai

Zhen-Jie Li

Jin Wang

Feng-Xian Yang

Xin Liu

Jing Li

Qian Gao

Xue-Mei Li

Yin-Ke Li

Wei-Guang Wang

Min Zhou

Qiu-Fen Hu

Archives of pharmacal research

ARCHIVES OF PHARMACAL RESEARCH 是韩国药学会的官方期刊，自 1976 年开始出版。ARCHIVES OF PHARMACAL RESEARCH 是一本跨学科期刊，致力于发表药物发现、药物开发、和药物行动，以提供关于药物和候选药物的基本和新颖的信息。

The Archives of Pharmacal Research is the official journal of the Korean Pharmaceutical Society, published since 1976. This interdisciplinary journal focuses on research in drug discovery, drug development, and drug action, aiming to provide fundamental and novel information about drugs and drug candidates.

《Archives of Pharmacal Research》是韩国药学会的官方期刊，自1976年开始出版。该期刊是一份跨学科的学术刊物，专注于药物发现、药物开发和药物作用的研究，旨在提供关于药物及其候选药物的基础和新颖的信息。

Archives of Pharmacal Research

Arch Pharm Res

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

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.

Category	Quartile
医学	3
医学, 药学	2
医学, 药物化学	3

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

ivySCI AI Smartly Parses PDF, Answers Researchers' Questions, and Helps You Understand Papers in Seconds

Journal Info

Category	Quartile
PHARMACOLOGY & PHARMACY	1