Design, Synthesis, and Bioactivity Study of Novel Tryptophan Derivatives Containing Azepine and Acylhydrazone Moieties

Abstract

Based on the scaffolds widely used in drug design, a series of novel tryptophan derivatives containing azepine and acylhydrazone moieties have been designed, synthesized, characterized, and evaluated for their biological activities. The bioassay results showed that the target compounds possessed moderate to good antiviral activities against the tobacco mosaic virus (TMV), among which compounds 5c, 6a, 6h, 6t, 6v, and 6y exhibited higher inactivation, curative, and protection activities in vivo than that of ribavirin (40 ± 1, 37 ± 1, 39 ± 2% at 500 mg/L). Especially, 6y showed comparable activities to that of ningnanmycin (57 ± 2, 55 ± 3, 58 ± 1% at 500 mg/L). Meanwhile, we were pleased to find that almost all these derivatives showed good larvicidal activities against Plutella xylostella. Meanwhile, these derivatives also showed a broad spectrum of fungicidal activities.

A Comprehensive Investigation of Hydrazide and Its Derived Structures in the Agricultural Fungicidal Field

“…Based on natural products bearing an azepine substructure, Wang's group reported the synthesis and bioactivity of novel azepine derivatives 72 containing acylhydrazone moiety. 78 The fungicidal assays indicated that these compounds showed moderate to good and selective inhibitory abilities against 14 phytopathogens at 50 μg/mL. For example, most compounds had inhibition rates exceeding 60% against F. moniliforme at 50 μg/mL.…”

Design, Synthesis and Various Bioactivity of Acylhydrazone-Containing Matrine Analogues

“…For example, β-tetrahydrocarboline acylhydrazone derivatives have excellent antiviral activity against the tobacco mosaic virus (TMV), good fungicidal activity and the most potent anti-TMV compound among them (later named chloroinconazide [ 11 ]) exhibited excellent anti-TMV activity in the field [ 12 ]. Moreover, oxindole spirocyclic acylhydrazone derivatives [ 13 ], trans-ferulic acid [ 14 ], indole [ 15 ], carbazole [ 16 ], tryptophan [ 17 ] and azepino [4,5-b]indole acylhydrazone derivatives [ 18 ] were also identified as novel anti-TMV agents. In addition, C8-acylhydrazone coumarin-type derivatives of osthole exhibited better insecticidal activity against Mythimna separata Walker [ 19 ], and quinoline derivatives with acylhydrazide were found to have novel antifungal activity [ 20 ] ( Figure 1 ).…”

Tandem (4 + 3)-Annulation of Aziridines: Stereoselective Access to Fused Azepinoindoles

“…Among the myriad of heterocycles constituting the core motif in natural products and pharmaceuticals, aza-heterocycles have been dynamically pursued and enjoy distinguished application in the field of chemical biology . Unambiguously, in this realm, the incessant identification of seven-membered aza-heterocycles has led to enduring progress that serves as a relevant guideline for the innovation of annulation strategies toward their comprehensive synthesis . Despite the traditional and well-established methods for the synthesis of five- and six-membered ring systems, the development of strategies for assembling seven-membered rings, especially N-heterocycles, remains relatively scarce. , This can be attributed to their relative instability, nonbonding interaction, and unfavorable enthalpic and entropic reasons .…”