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... mp: 195.4-196.2 • C. 1 H NMR (400 MHz, Acetone-d 6 ) δ 10.68 (s, 1H), 7.65 (s, 1H), 7.54-7.49 (m, 1H), 7.44 (dd, J = 7.9, 1.0 Hz, 1H), 7.36 (d, J = 7.2 Hz, 1H), 7.28-7.17 (m, 2H), 7.13-7.08 (m, 1H), 6.94 (dd, J = 8.3, 1.0 Hz, 1H), 6.85-6.80 (m, 1H), 6.71 (dd, J = 7.6, 1.7 Hz, 1H), 5.12 (s, 2H), 3.74 (s, 3H). 13 C NMR (100 MHz, DMSO-d 6 ) δ 156.5, 137.1, 136.3, 129.6, 127.8, 127.3, 126.9, 126.8, 125.3, 122.2, 122.1, 120.8, 120.1, 119.4, 112.4, 111.1, ...
Context 2
... 7.81 (s, 1H), 7.46 (d, J = 8.1 Hz, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.32 (d, J = 7.9 Hz, 1H), 7.18 (dt, J = 19.7, 7.7 Hz, 2H), 7.05 (t, J = 7.5 Hz, 1H), 6.90 (d, J = 8.2 Hz, 1H), 6.79 (t, J = 7.4 Hz, 1H), 6.57 (d, J = 7.5 Hz, 1H), 5.07 (s, 2H), 3.64 (s, 3H). 13 C NMR (100 MHz, DMSO-d 6 ) δ 156. 5, 138.4, 136.4, 129.5, 127.9, 127.0, 126.9, 125.3, 125.0, 122.1, 120.8, 120.1, 119.5, 115.5, 112.4, 111.1, ...
Context 3
... simulated models and scores indicated that streptochlorin binds with tLeuRS in a similar mode to AN2690. Streptochlorin formed two hydrogen bonds with residues Thr248 and Thr252, hydrophobic interactions with residues Arg249, Val340 and Asp344, and formed ion-π interactions with residue Arg346 (Figure 10). The calculated binding affinity of streptochlorin and AN2690-AMP based on dock score, residual interaction (Hbond, vdw, estat, dsolv) is shown in Table 3, and most of these data are very close, especially ΔE binding . ...
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... Screening conducted at Syngenta showed that pimprinine is active against a variety of phytopathogenic fungi when tested in liquid culture assays. In our earlier cooperative research with Syngenta, pimprinine was used as the lead structure to systematically optimize each site of its scaffold, including: the introduction of different halogens to the oxazole ring; 9 replacing the original oxazole ring with an imidazole ring and an oxadiazole ring; 10 introducing a bridge structure between the indole ring and oxadiazole ring; 11,12 changing the link site of the indole and oxazole rings; 13,14 and replacing indole rings with other active heterocycles. 15 We found that the indole ring is essential for the antifungal activity of these natural active compounds. ...
BACKGROUND
To obtain new environmentally friendly fungicides, we used the natural product pimprinine as the lead compound, and designed and synthesized two series of ring‐opening derivatives of pimprinine containing amide/thioamide. We then studied their antifungal activity against six common plant pathogenic fungi in vitro.
RESULTS
Most of the target compounds have good antifungal activity against six important plant pathogenic fungi in vitro. At a concentration of 50 μg ml⁻¹, compound 3o showed prominent antifungal effects on Alternaria solani and Rhioctornia solani, with inhibition rates of 91.8% and 97.4%, and a 50% effective concentration (EC50) of 6.2255 and 0.6969 μg ml⁻¹ respectively. The EC50 of compound 3o against Alternaria solani was significantly lower than that of boscalid (13.0380 μg ml⁻¹) and flutriafol (11.9057 μg ml⁻¹). In addition, compound 3o had good antifungal activity against Sclerotinia sclerotiorum, cucumber powdery mildew, cucumber Botrytis cinerea and Phytophthora capsici in vivo; the antifungal activity of compound 3o against cucumber Botrytis cinerea is 91.7%. At the same time, docking results for highly active compound 3o with the presumed target succinate dehydrogenase and the molecular docking prediction scores of all compounds further indicate its possible antifungal activity mechanism.
CONCLUSION
The designed and optimized derivative 3o of ring‐opening pimprinine has good antifungal activity and can be used as a new antifungal drug for further research. © 2023 Society of Chemical Industry.
... Meanwhile, pimprinine and streptochlorin lack potency under lower concentrations and are rarely extended to the next stage of study, as they are not potent enough to be used as antifungal agents, and the mode of action for their antifungal activity is still unclear. In our latest study on the structural optimizations including different modifications at the indole ring and oxazole ring [21][22][23][24][25][26], we found that the 5-(3′indolyl)oxazole core was the essential moiety for maintaining antifungal activity. In this study, as a continuation of our extensive research program to discover novel bioactive lead compounds, pimprinine and streptochlorin were used as the parent structures to carry out structural optimization ( Figure 2), with the structural features combination strategy of these two indole alkaloids. ...
... The mode of action for the antifungal activity of pimprinine and streptochlorin derivatives is still not clear, though it has been reported that pimprinine is a potent inhibitor of monoamine oxidase [28,29]. Molecular docking in our previous study indicated that a pimprinine and streptochlorin derivative binds with leucyl-tRNA synthetase in a similar mode as AN2690, offering a perspective on the potential target for the antifungal activity of this series of indole natural products [26]. ...
Pimprinine and streptochlorin are indole alkaloids derived from marine or soil microorganisms. In our previous study, they were promising lead compounds due to their potent bioactivity in preventing many phytopathogens, but further structural modifications are required to improve their antifungal activity. In this study, pimprinine and streptochlorin were used as parent structures with the combination strategy of their structural features. Three series of target compounds were designed and synthesized. Subsequent evaluation for antifungal activity against six common phytopathogenic fungi showed that some of thee compounds possessed excellent effects, and this is highlighted by compounds 4a and 5a, displaying 99.9% growth inhibition against Gibberella zeae and Alternaria Leaf Spot under 50 μg/mL, respectively. EC50 values indicated that compounds 4a, 5a, 8c, and 8d were even more active than Azoxystrobin and Boscalid. SAR analysis revealed the relationship between 5-(3'-indolyl)oxazole scaffold and antifungal activity, which provides useful insight into the development of new target molecules. Molecular docking models indicate that compound 4a binds with leucyl-tRNA synthetase in a similar mode as AN2690, offering a perspective on the mode of action for the study of its antifungal activity. These results suggest that compounds 4a and 5a could be regarded as novel and promising antifungal agents against phytopathogens due to their valuable potency.
A series of novel indole Schiff base derivatives (2a–2t) containing a 1,3,4-thiadiazole scaffold modified with a thioether group were synthesized, and their structures were confirmed using Fourier transformed-infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR), and high resolution-mass spectroscopy (HR-MS). In addition, the antifungal activity of synthesized indole derivatives was investigated against Fusarium graminearum (F. graminearum), Fusarium oxysporum (F. oxysporum), Fusarium moniliforme (F. moniliforme), Curvularia lunata (C. lunata), and Phytophthora parasitica var. nicotiana (P. p. var. nicotianae) using the mycelium growth rate method. Among the synthesized indole derivatives, compound 2j showed the highest inhibition rates of 100%, 95.7%, 89%, and 76.5% at a concentration of 500 μg/mL against F. graminearum, F. oxysporum, F. moniliforme, and P. p. var. nicotianae, respectively. Similarly, compounds 2j and 2q exhibited higher inhibition rates of 81.9% and 83.7% at a concentration of 500 μg/mL against C. lunata. In addition, compound 2j has been recognized as a potential compound for further investigation in the field of fungicides.
