Design, Synthesis, and Bioactivity of Aldisine Derivatives Containing Oxime and Hydrazine Moieties Based on Hydrogen Bonds

Marine natural products have attracted more and moreattentionin drug research and development due to their unique structure, diversebiological activities, and novel mode of action. Using antiviral alkaloidaldisine as the lead compound and drawing on the hydrogen bond effectwidely used in drug design, derivatives containing oxime and hydrazonemoieties were designed and synthesized by introducing functional groupswith hydrogen-bond receptors or donors into molecules. The configurationof derivatives was systematically studied through nuclear Overhausereffect (NOE) spectroscopy and single crystal analysis. The antiviralactivity test result showed that most derivatives had antiviral activityagainst tobacco mosaic virus (TMV), and some compounds had betteractivity than the commercial antiviral drug ribavirin, especiallycompounds 2 and 24, which had comparableactivity to the most effective commercial antiviral drug ningnanmycin.Preliminary mode of action studies showed that compound 2 could affect the assembly of rod-shaped TMVs by promoting the aggregationand fragmentation of TMV coat proteins. Molecular docking experimentsdemonstrated that the introduction of oxime and hydrazone moietiescould indeed increase the hydrogen bond between molecules and targetproteins. In addition, we conducted fungicidal and larvicidal activitiesstudy of these derivatives. Most of these derivatives had good larvicidalactivities against Mythimna separata and Plutella xylostella and showedbroad-spectrum fungicidal activities.

Automated summary

Marine natural products have become increasingly important in drug research and development because of their unique structure, diverse biological activities, and novel mode of action. This study focused on designing and synthesizing derivatives of antiviral alkaloidal disine by introducing hydrogen-bond receptors or donors into molecules. The derivatives exhibited antiviral activity against tobacco mosaic virus (TMV), with some compounds showing better activity than the commercial antiviral drug ribavirin. Additionally, the derivatives demonstrated larvicidal and broad-spectrum fungicidal activities, making them potential candidates for further investigation.