- Optimization, Structure-Activity Relationship, and Mode of Action of Nortopsentin Analogues Containing Thiazole and Oxazole Moieties
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Plant diseases seriously endanger plant health, and it is very difficult to control them. A series of nortopsentin analogues were designed, synthesized, and evaluated for their antiviral activities and fungicidal activities. Most of these compounds displayed higher antiviral activities than ribavirin. Compounds 1d, 1e, and 12a, with excellent antiviral activities, emerged as novel antiviral lead compounds, among which 1e was selected for further antiviral mechanism research. The mechanism research results indicated that these compounds may play an antiviral role by aggregating viral particles to prevent their movement in plants. Further fungicidal activity tests revealed that nortopsentin analogues displayed broad-spectrum fungicidal activities. Compounds 2p and 2f displayed higher antifungal activities against Alternaria solani than the commercial fungicides carbendazim and chlorothalonil. Current research has laid a foundation for the application of nortopsentin analogues in plant protection.
- Guo, Jincheng,Hao, Yanan,Ji, Xiaofei,Wang, Ziwen,Liu, Yuxiu,Ma, Dejun,Li, Yongqiang,Pang, Huailin,Ni, Jueping,Wang, Qingmin
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p. 10018 - 10031
(2019/10/05)
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- Agonists for the adenosine A1 receptor with tunable residence time. a case for nonribose 4-amino-6-aryl-5-cyano-2-thiopyrimidines
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We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A 1 receptor (hA1AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, that is, the potential elimination of slightly less active compounds that may display preferable binding kinetics.
- Louvel, Julien,Guo, Dong,Agliardi, Marta,Mocking, Tamara A. M.,Kars, Roland,Pham, Tan Phát,Xia, Lizi,De Vries, Henk,Brussee, Johannes,Heitman, Laura H.,Ijzerman, Adriaan P.
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supporting information
p. 3213 - 3222
(2014/05/20)
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- Optimizing thiadiazole analogues of resveratrol versus three chemopreventive targets
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Chemoprevention is an approach to decrease cancer morbidity and mortality through inhibition of carcinogenesis and prevention of disease progression. Although the trans stilbene derivative resveratrol has chemopreventive properties, its action is compromised by weak non-specific effects on many biological targets. Replacement of the stilbene ethylenic bridge of resveratrol with a 1,2,4-thiadiazole heterocycle and modification of the substituents on the two aromatic rings afforded potential chemopreventive agents with enhanced potencies and selectivities when evaluated as inhibitors of aromatase and NF-κB and inducers of quinone reductase 1 (QR1).
- Mayhoub, Abdelrahman S.,Marler, Laura,Kondratyuk, Tamara P.,Park, Eun-Jung,Pezzuto, John M.,Cushman, Mark
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experimental part
p. 510 - 520
(2012/03/10)
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