Splicing Indoles and 4,5-Dihydro-1H-pyrazoline Structure Gave Birth to Novel Antiviral Agents: Design, Synthesis, and Mechanism Study

Abstract

The specific conation of our research is to invent a series of indole derivatives containing a 4,5-dihydro-1H-pyrazoline motif with effective antiviral activity. The anti-potato virus Y (PVY) activities of target compounds were systematically investigated. Most target compounds exhibited good PVY activities. Compound D40, which exhibited outstanding anti-PVY activities, was sieved using a three-dimensional quantitative structure–activity relationship. Based on the anti-PVY activity assessments, the curative and protective activities of D40 were found to be 64.9 and 60.8%, respectively, which were superior to those of the commercial drug Ningnanmycin (50.2 and 50.7%, respectively). In addition, defensive enzyme activities and proteomics results indicate that D40 can increase the three crucial defense-related enzyme activities and regulate the carbon fixation pathway in photosynthetic organisms to intensify the resistance of plants to PVY. Therefore, our study suggests that compound D40 might be used as a suitable crop protection pesticide.

Tryptanthrin Derivative B1 Binds Viral Genome-Linked Protein (VPg) of Potato Virus Y

“…We conducted the interaction studies using a Nano Temper Monolith NT.115 (Nano Temper, Munich, Germany) MST apparatus and labeled the target proteins using a Monolith NT RED-NHS second-generation labeling kit following the manufacturer's protocol. We prepared the small molecule compounds, performed the pre-experimental setup, and processed experimental data following the experimental method described by Wang et al 28 We performed ITC binding measurements using an isothermal titration calorimeter (ITC200 GE Healthcare, Boston, MA) at 25 °C in a Q-B buffer. Before the experiment, we cleaned the apparatus using the method outlined by Bai et al 29 We performed the experiment with 0.1 mM VPg protein and 1 mM candidate compound.…”

“…It helps hosts develop resistance by affecting the polymerization of viral proteins, thus inhibiting viral assembly and reducing pathogenicity. Therefore, we selected it as a positive control agent in this study. − …”

Discovery of Novel Oxathiapiprolin Derivatives as Potent Fungicide Candidates

“…Our previous study showed that the binding site space for the pyrazole group in OXA could accommodate larger molecular fragments. As we know, the indole ring is a functional and versatile fragment that has been widely applied in drug and pesticide design. − Some of representative compounds ( compound 15–31 − containing the indole ring are shown in Figure S1. Here, to continue our research on OXA, an indole fragment was introduced into OXA to replace the pyrazole ring (Figure ).…”

Design, Synthesis, Antimicrobial Properties, and Molecular Docking of Novel Furan-Derived Chalcones and Their 3,5-Diaryl-∆2-pyrazoline Derivatives

“…Chalcones have been reported to exhibit a wide range of pharmacological activities such as antimicrobial [10][11][12][13], anticancer [14][15][16], anti-inflammatory [17][18][19], antiviral [20], and antioxidant [21,22]. Furthermore, heterocyclic compounds each bearing a pyrazoline scaffold have been reported as antimicrobial [23][24][25], anticancer [26][27][28], anti-inflammatory [29][30][31], antiviral [32], and antioxidant [33].…”

“…matory [17][18][19], antiviral [20], and antioxidant [21,22]. Furthermore, heterocyclic compounds bearing pyrazoline scaffolds have been reported as antimicrobial [23][24][25], anticancer [26][27][28], anti-inflammatory [29][30][31], antiviral [32], and antioxidant [33].…”