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

Abstract

Marine natural products have attracted more and more attention in drug research and development due to their unique structure, diverse biological activities, and novel mode of action. Using antiviral alkaloid aldisine as the lead compound and drawing on the hydrogen bond effect widely used in drug design, derivatives containing oxime and hydrazone moieties were designed and synthesized by introducing functional groups with hydrogen-bond receptors or donors into molecules. The configuration of derivatives was systematically studied through nuclear Overhauser effect (NOE) spectroscopy and single crystal analysis. The antiviral activity test result showed that most derivatives had antiviral activity against tobacco mosaic virus (TMV), and some compounds had better activity than the commercial antiviral drug ribavirin, especially compounds 2 and 24, which had comparable activity 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 aggregation and fragmentation of TMV coat proteins. Molecular docking experiments demonstrated that the introduction of oxime and hydrazone moieties could indeed increase the hydrogen bond between molecules and target proteins. In addition, we conducted fungicidal and larvicidal activities study of these derivatives. Most of these derivatives had good larvicidal activities against Mythimna separata and Plutella xylostella and showed broad-spectrum fungicidal activities.

Design and Enantioselective Synthesis of Chiral Pyranone Fused Indole Derivatives with Antibacterial Activities against Xanthomonas oryzae pv oryzae for Protection of Rice

“…The title fused indole derivatives ( 5a–5q ) for antibacterial activities were readily prepared from aldehydes 4 and isatin-derived α,β-unsaturated ester 3a , which was obtained from a Wittig reaction and N -protection sequence (Figure A), as the starting materials (Figure B). The preparation involves a one-pot operation developed in our laboratory through an enantioselective organocatalytic [4 + 2] annulation . Currently, our focus was directed toward assessing the impact of various substituents on the biological activity of the resulting products 5 , in particular, to study how the molecular chirality and functional moieties incorporated in the fused indole scaffold influenced the antibacterial activity.…”

“…The structural derivatization and optimization studies on naturally occurring biologically active molecules as potential leads have emerged as an appealing strategy for the discovery and development of novel green pesticides. − Research reveals that certain natural products or their derivatives featuring indole structures demonstrate commendable biological activity while with low toxicity toward nontarget organisms and environment . Noteworthy examples include indole-3-butyric acid, ethychlozate, and indometacin. − Similarly, natural molecules with pyran moieties, such as indole-3-butyric acid, ethychlozate, indometacin, viridepyronone, coumarins, chromone, and osthole, show significant biological activity that could be applied in combating pathogenic microorganisms. − …”

Discovery of Novel Acethydrazide-Containing Flavonol Derivatives as Potential Antifungal Agents

“…Phytopathogenic fungi pose a significant threat to agricultural productivity and ecosystem health. They infect various parts of plants, including the leaves, stems, roots, and fruits, leading to devastating crop yield losses. − To mitigate agricultural losses caused by pathogenic fungi, fungicides have been widely employed as a protective strategy in agricultural practices. − Succinate dehydrogenase (SDH) serves as an ideal target for fungicides, and SDH inhibitors (SDHIs) exert their antifungal activity by disrupting the mitochondrial tricarboxylic acid cycle and respiratory chain. − The antifungal mechanism of SDHIs makes them a class of effective fungicides. However, long-term application of SDHIs can lead to reduced efficacy, plant toxicity, and environmental pollution .…”

Design, synthesis and insecticidal activity of novel Isoxazoline Acylhydrazone compounds

“…[22][23][24][25][26][27] The capacity of acylhydrazone to function as both a hydrogen bond donor and acceptor can potentially augment the intermolecular interactions between the agents and their respective molecular targets. 28,29 In the design of new pesticides, there are several important methods including 'bioisosteric', 'scaffold hopping' and 'mix and match'. [30][31][32][33] In this study, a new series of isoxazoline derivatives containing an acylhydrazone fragment was designed and synthesized (Fig.…”