Discovery of Tryptanthrins as Novel Antiviral and Anti-Phytopathogenic-Fungus Agents

Abstract

Plant diseases seriously affect the yield and quality of crops and are difficult to control. Tryptanthrin and its derivatives (tryptanthrins) were synthesized and evaluated for their antiviral activities and fungicidal activities. We found that tryptanthrins have good antiviral activities against tobacco mosaic virus (TMV) for the first time. Most of the tryptanthrins showed higher anti-TMV activities than that of ribavirin (inhibitory rates of 40, 37, and 38% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively). Compound 3n (inhibitory rates of 52, 49, and 54% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively) and compound 14 (inhibitory rates of 51, 48, and 53% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively) emerged as new antiviral lead compounds with excellent antiviral activities. Compound 16 was selected for further antiviral mechanism research, which revealed that compound 16 could inhibit virus assembly by decomposing 20S coat protein (CP) disk. Molecular docking results showed that compounds 3n and 14, which have higher antiviral activities in vivo than that of compound 16, do show stronger interaction with TMV CP. Further fungicidal activity tests showed that tryptanthrins displayed broad-spectrum fungicidal activities, especially for compound 16. These compounds showed good selectivity to Physalospora piricola. In the current study, a small molecular library of tryptanthrin was constructed and the bioactivity spectrum of these compounds was broadened, which lays a foundation for their application in plant protection.

Identification of Carbazole Alkaloid Derivatives with Acylhydrazone as Novel Anti-TMV Agents with the Guidance of a Digital Fluorescence Visual Screening

“…For the substitution on the aromatic ring of position R 2 , hydroxy group is beneficial for the antiviral activity, and the electron-withdrawing groups at the same position benefit the antiviral activity. Hao et al also found that the substitution by an electron-withdrawing group improved the biological activity of tryptanthrin derivatives …”

“…Hao et al also found that the substitution by an electron-withdrawing group improved the biological activity of tryptanthrin derivatives. 36 3.4. Effects of Compounds 5 and 11 on Root Length, Bud Length, Dry Weight, and Phytotoxic Activity of N. benthamiana.…”

Synthesis of N‐Fused Indolines via Copper (II)‐Catalyzed Dearomatizing Cyclization of Indoles

“…Moreover, 7 aa can be oxidized to obtain alkaloid tryptanthrin ( 8 aa ). Its antiviral activities have been studied recently [15] . The carbonyl group and C−N bond of 7 aa can be selectively reduced by employing B(C 6 F 5 ) 3 and NH 3 ‐BH 3 to generate the indoline product 9 aa .…”

Catalyst‐Free One‐Pot Multi‐Component Synthesis of 2‐Substituted Quinazolin‐4‐carboxamides from 2‐Aminophenyl‐2‐oxoacetamides, Aldehydes, and Ammonium Acetate

“…A majority of substituted quinazoline derivatives are known for their broad-spectrum biological activities including anticancer (tyrosine kinase inhibitors), antiviral, anti-inflammatory, antiprotozoan, antifungal, antibacterial, diuretics, antimalarial, antidepressant, muscle relaxants, antitubercular, anticonvulsant and many more. [1][2][3][4][5][6][7][8][9][10][11][12] Among the 4-substituted quinazolines, 4-amino and 4-phenoxy derivatives have been known to constitute an active class of drugs [13] and other materials, [14] while on the other hand, the 4-carbonyl derivatives of quinazoline such as quinazolin-4-carboxamides have not explored well so far despite exhibiting variety of biological properties such as potent inhibitor of AAKl, acetyl CoA carboxylase inhibitor, anti-disorders, adenosine receptors, anti-neurodegenerative, and anticancer have been described (Figure 1). [15][16][17][18][19][20] In the past few decades, the catalytic one-pot multicomponent reactions has become a powerful tool for the synthesis of N-containing biologically active heterocycles.…”