Discovery of N-(4-fluoro-2-(phenylamino)phenyl)-pyrazole-4-carboxamides as potential succinate dehydrogenase inhibitors.
Pestic Biochem Physiol
; 158: 175-184, 2019 Jul.
Article
in En
| MEDLINE
| ID: mdl-31378354
ABSTRACT
Succinate dehydrogenase (SDH), an essential component of cellular respiratory chain and tricarboxylic acid (or Krebs) cycle, has been identified as one of the most significant targets for pharmaceutical and agrochemical. Herein, with the aim of discovery of new antifungal lead structures, a class of novel N-(4-fluoro-2-(phenylamino)phenyl)-pyrazole-4-carboxamides were designed, synthesized and evaluated for their biological activities. They were bioassayed against seven phytopathogenic fungi, Rhizoctonia solani, Phytophthora infestans, Fusarium oxysporum f. sp. vasinfectum, Botryosphaeria dothidea, Gibberella zeae, Alternaria alternate and Fusarium oxysporum f. sp. niveum. The results indicated that most of the compounds displayed good antifungal activities, especially against R.â¯solani. Among them, compounds 7 and 12 exhibited higher antifungal activities against R.â¯solani in vitro with EC50 value of 0.034â¯mg/L and 0.021â¯mg/L, being superior to the commercially available fungicide bixafen (EC50â¯=â¯0.043â¯mg/L). Pot tests against R.â¯solani showed that in vivo EC50 values of compounds 7 (2.694â¯mg/L) and 12 (2.331â¯mg/L) were higher than that of bixafen (3.724â¯mg/L). In addition, inhibitory activity of compound 12 against SDH indicated compound 12 (IC50â¯=â¯1.836â¯mg/L) showed good inhibitory activity against SDH, being close to bixafen's inhibitory activity (IC50â¯=â¯1.222â¯mg/L). And, molecular modeling of the SDH-compound 12 complex suggested that compound 12 could strongly bind to and interact with the binding site of the SDH. The results of the present work showed that N-(4-fluoro-2-(phenylamino)phenyl)-pyrazole-4-carboxamides were a new fungicides for discovery of SDH inhibitors and worth further study.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Succinate Dehydrogenase
/
Antifungal Agents
Language:
En
Journal:
Pestic Biochem Physiol
Year:
2019
Document type:
Article