Novel carboxylated pyrroline-2-one derivatives bearing a phenylhydrazine moiety: Design, synthesis, antifungal evaluation and 3D-QSAR analysis. Issue 21 (1st November 2020)

• Record Type: Journal Article
• Authors: Chen, Min; Zhang, Lizhi; Lu, Aimin; Wang, Xiaobin; Si, Weijie; Yan, Jinghua; Yang, Chunlong
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 21(2020)
• Publication Date: 2020-11-01
• Subjects: Pyrroline-2-one -- Phenylhydrazine -- Lead optimization -- Antifungal activity -- 3D-QSAR; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127519
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Novel pyrroline-2-one derivatives were designed and synthesized based on natural tetramic acids. Some compounds showed excellent antifungal activity. 3D-QSAR provided valuable information for further structural optimization. Highlights: Novel carboxylated pyrroline-2-ones bearing a phenylhydrazine moiety were synthesized. Most compounds possessed antifungal effects with EC50 values of less than 1 μg/mL. 6u was obviously effective in controlling fusarium head blight and rice sheath blight. Target compounds have excellent and broad-spectrum antifungal effects. 3D-QSAR model provide suggestions for modification to improve antifungal activity. Abstract: Aiming to discover novel high-efficient antifungal leads that possess an innovative action mechanism, twenty-three carboxylated pyrroline-2-one derivatives, bearing a phenylhydrazine moiety, were rationally designed and firstly prepared in this letter. The in vitro bioassays showed that most of the compounds possessed excellent antifungal effects with the EC50 values of less than 1 μg/mL against the phytopathogenic fungi Fusarium graminearum ( Fg ), Botrytis cinerea ( Bc ), Rhizoctonia solani ( Rs ) and Colletotrichum capsici ( Cc ). The further bioassays showed that the compound 6u showed the comparable in vivo control effect with carbendazim against fusarium head blight and rice sheath blight. The 3D-QSAR model revealed the pivotal effects of a bulky electron-donating group at the 1-position of pyrrole ring, a bulky electron-withdrawing group at the 4-position of phenyl ring and a small alkyl at the carbonate group on the anti- Rs activities of target compounds. The abnormal mycelial morphology and delayed spore germination were observed in the treatments of compound 6u . Given the excellent and broad-spectrum antifungal effects the target compounds have, we unfeignedly anticipated that the above finding could motivate the discovery of high-efficient antifungal leads, which might possess an innovative action mechanism against phytopathogenic fungi.