Chinese Journal of Organic Chemistry >
Design, Synthesis and Biological Activity of Myricetin Derivatives Containing 1,2,4-Triazolo[3,4-b]-1,3,4-thiadiazole
Received date: 2022-09-25
Revised date: 2022-10-22
Online published: 2022-11-22
Supported by
National Natural Science Foundation of China(21867003); Science Fund of Guizhou Province(20192452)
A series of myricetin derivatives containing 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole moiety were designed and synthesized using myricetin as the starting material through active splicing strategy. All target compounds were characterized by 1H NMR, 13C NMR and high-resolution mass spectra (HRMS). Single crystal X-ray diffraction experiments were carried out with 3-(3-((3-ethyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)thio)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H- chromen-4-one (A5). When the concentration was 100 μg/mL, the inhibition rate of 3-(3-((3-(4-(tert-butyl)phenyl)-[1,2,4]- triazolo[3,4-b][1,3,4]thiadiazol-6-yl)thio)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A15) agai- nst Xanthomonas axonopodis pv.citri (Xac) was 63.3%, which was better than that of the control drug thiophanate-copper (57.3%). Biological activity test results that these compounds showed good inhibitory activity against tobacco mosaic virus (TMV). Among them, in terms of therapeutic activity, the EC50 values of compounds A5, 5,7-dimethoxy-3-(4-((3-(methoxy- methyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)thio)butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A8), 5,7-di- methoxy-3-(3-((3-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)thio)propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen- 4-one (A9), and 5,7-dimethoxy-3-(4-((3-(p-tolyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)thio)butoxy)-2-(3,4,5-trimethoxy- phenyl)-4H-chromen-4-one (A12) were 88.3, 139.1, 109.9, 160.1 μg/mL, respectively, which were better than the control drug ningnanmycin (227.2 μg/mL). In terms of protective activity, the EC50 values of compounds 5,7-dimethoxy-3-(4-((3-phenyl- [1,2,4]-triazolo[3,4-b][1,3,4]thiadiazol-6-yl)thio)butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A10), 5,7-dimeth- oxy-3-(4-((3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)thio)butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chro- men-4-one (A14), A15, 3-(4-((3-(4-(tert-butyl)phenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)thio)butoxy)-5,7-dimeth- oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A16), and 3-(4-((3-(4-chlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thia- diazol-6-yl)thio)butoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A18) were 103.1, 107.4, 86.3, 79.2, 111.5 μg/mL, respectively, which were better than the control drug ningnanmycin (179.2 μg/mL). Microscale thermophoresis (MST) indicated that compounds A12 and A16 have strong binding force to tobacco mosaic virus coat protein (TMV-CP). Molecular docking experiments showed that compound A16 has a strong interaction with TMV-CP.
Qifan Wang , Yuanquan Zhang , Li Xing , Yuanxiang Zhou , Chenyu Gong , Bangcan He , Nian Zhang , Yongjun Wu , Wei Xue . Design, Synthesis and Biological Activity of Myricetin Derivatives Containing 1,2,4-Triazolo[3,4-b]-1,3,4-thiadiazole[J]. Chinese Journal of Organic Chemistry, 2023 , 43(4) : 1525 -1536 . DOI: 10.6023/cjoc202209030
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